Anp1105 Midterm 1 Notes PDF

Midterm 1- Anatomy and Physiology Notes Human Anatomy and Physiology I (University of Ottawa) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by swim lowmess ([email protected]) ...

Midterm 1- Anatomy and Physiology Notes Human Anatomy and Physiology I (University of Ottawa) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by swim lowmess ([email protected])  Human Anatomy and Physiology Notes Lecture 1- Introduction, Structure, Function and Cell Theory Overview When referring to anatomy/Physiology of the body, we assume that we are talking about a healthy 22-year old male weighing 155 lbs or a health young female weighing 125 lbs Topics of Anatomy Is the study of the structure of body parts Must memorize Major subdivisions of anatomy are: ○ Gross anatomy- the study of large body structures Regional anatomy- study of structures in particular region Systematic anatomy- body structure is studied system by system Surface anatomy- study of internal structures as they relate to the overlying skin surface ○ Microscopic anatomy- study of structures that can’t be seen with naked eye Cytology- considers cells of body Histology- the study of tissues ○ Developmental anatomy- traces structural changes that occur in body throughout lifespan Embryology- study of developmental changes that occur before birth Topics of Physiology Physiology is the study of the functions of the body Must understand Subdivisions concern the individual specific organ systems ○ Eg; neurophysiology, cardiovascular physiology, etc. Often focuses on events at a cellular/molecular level Complementarity of Structure and Function Anatomy and physiology is inseparable as function always reflects structure This key concept is called the principle of complementarity of structure and function You can infer function from structure Scientific Reductionism Reductionism- an approach to understanding the nature of complex things by reducing them to simpler things Physiology often focuses on events at the cellular or molecular level because the body’s abilities depend on individual cells Downloaded by swim lowmess ([email protected]) Levels of Structural Organization Body’s organization ranges from atoms (smallest unit) to the entire organism (largest unit) Levels of structural organization (simplest to most complex): chemical, cellular, tissue, organ, organ system and organismal ○ Chemical level- atoms combine to form molecules ○ Cellular level- Cells are made up of molecules ○ Tissue level- Groups of similar cells with a common function 4 types- epithelial, muscle, connective, and nervous ○ Organ level- Structure composed of two (usually 4) tissue types. Specialized functional structure for specific activity ○ Organ System level- organs work together to accomplish a common purpose ○ Organismal level- An organism is made up of numerous organ systems Organ Systems of the Body Organ System Function Integumentary Forms external body covering + protects deep tissues from System injury Synthesizes vitamin D and houses external stimuli receptors and sweat and oil glands Hair, nails, skin Skeletal System Protects + supports organs Provides framework that muscles use for movement Blood cells synthesized in bones and bones store minerals Muscular System Allows manipulation of the environment, locomotion and facial expression Maintains posture + produces heat Nervous System Fast- acting control system of body Responds to external and internal stimuli by activating appropriate muscles and glands Endocrine System Glands secrete hormones which regulate numerous body processes Cardiovascular Blood vessels transport blood and other nutrients to the body System Heart pumps the blood Lymphatic System Picks up fluid leaked from blood vessels and returns it to blood Disposes of debris in the lymphatic stream Houses white blood cells (lymphocytes) involved in immunity Respiratory Keeps blood supplied with oxygen + removed carbon dioxide Downloaded by swim lowmess ([email protected])  System Gas exchange occurs through walls of air sacs in lungs Digestive System Breaks down food to be absorbed by blood Indigestible foods eliminated as feces Urinary System Eliminates nitrogenous wastes from body Regulates water, electrolyte and acid-base balance of the blood Reproductive Male and female System Used for production of offspring Parts of a Cell: Structure and Function Refer to the following lecture 1 powerpoint for condensed chart https://uottawa.brightspace.com/d2l/le/content/117592/viewContent/2387015/View Organelles In The Cytoplasm Is the region between nuclear and plasma membranes Consists of cytosol, organelles and inclusions (stored nutrients, secretory products, pigment granules) Organelle Structure Function Mitochondria Rodlike, double-membrane Site of ATP synthesis structure Powerhouse of the cell Outer membrane is smooth Has own DNA and replicates Inner membrane folded into independently projections called cristae Gel-like matrix in the center Ribosomes Consist of 2 subunits, each Synthesize proteins for various cell composed of ribosomal RNA and needs protein Can switch back and forth between free Free or attached to rough ER floating and bounded states Rough ER Outer surface is covered in External face synthesizes proteins ribosomes Integral proteins and phospholipids are Membranous also manufactured Coils through the cytoplasm Proteins are bound in vesicles and transported to the Golgi apparatus and other sites Smooth ER Is continuous with rough ER Does not make proteins Membranous system of sacs and Contains enzymes that are responsible tubules for synthesizing lipids and steroids, No ribosomes lipid metabolism and drug Downloaded by swim lowmess ([email protected])  detoxification Golgi Stack of flattened membranes and Packages, modifies and segregates Apparatus vesicles proteins and lipids made in the rough Located near the nucleus ER for secretion from the cell, inclusion in lysosome and incorporation in plasma membrane Peroxisomes Membranous sacs of catalase and Oxidase enzyme detoxifies many toxic oxidase enzymes substances and neutralizes free radicals Catalase (important enzyme) breaks down hydrogen peroxide Lysosomes Membranous sacs containing acid Sites of intracellular digestion hydrolases Work best in acidic conditions Spherical Microtubules Cylindrical Support cell and gives it shape Composed of tubulin proteins Involved in intracellular and cellular movements Form centrioles, cilia and flagella Microfilament Fine filaments composed of Involved in muscle contraction and s protein actin other intracellular movements Helps form cell’s cytoskeleton Intermediate Protein fibers Make up the stable cytoskeleton Filaments Composition varies Resist mechanical forces acting on cell Centrioles Paired cylindrical bodies Organize microtubule network during Each composed of nine triplets of mitosis to form the spindle and asters microtubules Form the bases of cilia and flagella Inclusions Varied Are storage for nutrients, wastes and cell products Cellular Extensions Part Structure Function Cilia Short, cell surface projections Their coordinated movement Composed of nine pairs of creates a current that propels microtubules surrounding a substances across cell surfaces central pair Flagellum Like cilium, but longer Propels the cell in its Only present in sperm cells in environment humans Downloaded by swim lowmess ([email protected])  Microvilli Tubular extensions of plasma Increase surface area for membrane absorption Contain bundle of actin fibers Parts Of The Nucleus Part Structure Function Nucleus Largest organelle Control center of cell Surrounded by nuclear envelope Transmits genetic information Contains fluid nucleoplasm, nucleoli Provides instructions for protein and chromatin synthesis Nuclear Double membrane Separates nucleoplasm from Envelope Porous cytoplasm Outer membrane is continuous with ER Regulates passage of substances to and from the nucleus Nucleolus Dense, spherical bodies Site of ribosome subunit synthesis Non-membrane bound Composed of RNA and proteins Chromatin Granular and threadlike Fundamental units are nucleosomes Composed of 30% DNA, 60% histone Packs DNA into a small volume to proteins and 10% RNA chains fit the nucleus Protects DNA structure and sequence Maintaining life Necessary Life Functions ○ All organisms carry out specific vital functional activities necessary for life ○ Include maintenance of boundaries, movement, digestion, responsiveness, metabolism, excretion, reproduction and growth Survival Needs -Requirements for maintaining life ○ Nutrients- taken through diet. Contain chemical substances required for energy and cell building ○ Oxygen- chemical reactions that release energy from foods are oxidative reactions that require oxygen ○ Water- accounts for 60-80% of body weight. Provides necessary environment for chemical reactions ○ Body Temperature- Normal body temperature is required for chemical reactions to occur. Muscular system activity generates the most heat. ○ Atmospheric Pressure- breathing and gas exchange are dependent on appropriate atmospheric pressure. Downloaded by swim lowmess ([email protected])  Lecture 2- Types of Tissues Processes Needed to Make Us Multicellular Cell division Work with environment Movement Cell differentiation Cell-Cell interactions ○ Direct interactions, endocrine and nervous system signal interactions Tissues Are groups of cells that are similar in structure and perform a common function Are four basic types of tissues in the body ○ Epithelial, connective, nervous and muscle tissue In short, epithelial tissue covers, connective tissue supports, nervous tissue controls and muscle tissue provides movement Overview of 4 Basic Tissues Tissue Function Location Nervous Tissue Internal communication Brain, spinal cord, nerves Muscle Tissue Contracts to cause movement Skeletal muscles Cardiac muscles Muscles of the walls of hollow organs (smooth muscles) Epithelial Forms boundaries, protects, secrets, Lining of digestive track and hollow Tissue absorbs, filters organs Glands Skin Surface Connective Supports, protects, binds other tissues Bones, tendons, fat and other soft Tissue together padding tissue Preparing Human Tissues for Microscopy Histology- the study of tissues Microscopy allows for the study of tissue structure Before viewing, the specimen must undergo the following steps in order; ○ It must be fixed (preserved) ○ Then, it must be cut into sections (slices) thin enough to transmit light/electrons ○ Finally, it must be stained to enhance contrast (light microscopy) Transmission electron microscopy (TEM) Downloaded by swim lowmess ([email protected])  ○ Tissue sections are stained with heavy metal salts that deflect electrons in the beam to different extents, providing contrast Scanning electron microscopy (SEM) ○ Provided 3-D pictures of an unsectioned tissue surface Type 1- Epithelial Tissue Is a sheet of cells that covers a body surface or lines a body cavity Two forms occur in the body ○ Covering and lining epithelium Forms outer layer of the skin Lines the open cavities of the urogenital, digestive and respiratory systems Covers the walls and organs of the closed ventral body cavity ○ Glandular epithelium Covers the glands of the body Secretory tissue in glands (eg; salivary glands) All substances received or given off by the body have to pass through the epithelium ○ Selective barrier- intestinal epithelium allows passage of certain substances Bidirectional, highly regulated in healthy and not healthy tissue Gut microbiome Accomplishes many functions including; ○ Protection, absorption, secretion, filtration, excretion, sensory reception Special Characteristics of Epithelium Has five distinguishing characteristics ○ Polarity, specialized contacts, supported by connective tissue, avascular but innervated, ability to regenerate Polarity ○ Apical surface (top) is exposed to surface or cavity Most are smooth, but some have microvilli (increases surface area) or cilia ○ Basal surface (bottom), faces inwards towards body Attached to basal lamina, an adhesive sheet that holds the basal surface of epithelial cells to underlying cells Acts as a selective filter that determines which molecules diffusing from underlying tissue are allowed in ○ Cell polarity is crucial for normal cell physiology and tissue homeostasis Specialized Intercellular Contacts ○ Cells need to fit closely together to form barrier ○ Specialized contact points bind adjacent epithelial cells together (between cells) ○ Lateral contacts include; Tight junctions- prevents substances from leaking between cells (regulated) Adherens junctions- mediate cell-cell adhesion via protein cadherins Downloaded by swim lowmess ([email protected])  Desmosomes- prevents cells from pulling apart in tissues subjected to mechanical stress (made up of protein desmoglein) Gap junctions- mediated by connexions. Intercellular communication. ○ Use different connecting proteins and attach to different filaments Supported by Connective Tissue ○ All epithelia have a basement membrane (BM) reinforces , resists stretching, tearing Defines epithelial boundary Consists of Basal lamina- layer of extracellular matrix (ECM) proteins Reticular lamina- deep to the basal lamina. Network of collagen III fibers ○ Disease Relevance- cancerous epithelial cells can penetrate BM and invade underlying tissues, resulting in spread of cancer (metastasis)---> 90% of cancer deaths Avascular, But Innervated ○ Avascular- no blood vessels Nutrients and oxygen diffuse from connective tissue ○ Innerved- have nerves Regeneration ○ Epithelials cells have high regenerative capacities ○ Simulated by loss of apical-basal polarity and broken lateral contacts ○ Some cells exposed to friction, hostile substances ----> damage Must be replaced Requires adequate nutrients and cell division Wound healing Classification of Epithelia Based on two factors Number of cell layers (1 or more) ○ Simple epithelia- a single layer thick ○ Stratified epithelia- are two or more layers thick Protection is a major role New cells regenerate from below Basal cells divide and migrate to surface More durable than simple epithelia Shape of cells ○ Squamous: flattened and scale-like (humans have a lot of them) Most of the cells in the outer layer of skin Passages of respiratory and digestive tracts Lining of hollow organs ○ Cuboidal: box-like, cube Downloaded by swim lowmess ([email protected])  ○ Columnar: tall, column-like In stratified epithelia, shape can vary in each layer, so classified according to shape in apical layer Types of Simple Epithelium Type and Image Description Function Location Simple Squamous -Single layer of flattened cells. -Allows materials to pass via -Kidney glomeruli -Disk shaped nuclei diffusion and filtration in sites -Air sacs of lungs -Sparse cytoplasm where protection is not key, but -Lining of heart -Simplest of epithelia rapid diffusion is. -blood vessels -Two types based on location -Secretes lubricating substances -lymphatic vessels *(see bottom for note)* in serosae (lining of ventral body -Serosae cavity) Simple Cuboidal -Single layer of cube like cells -Secretion and absorption -Kidney tubules -spherical central nuclei --Ducts and secretory portions of small glands -Ovary surface Simple Columnar -Single layer of tall cells with -Absorption -Non-ciliated line round to oval nuclei -Secretion of mucous, enzymes most of digestive -Many have microvilli and other substances tract (stomach to -Some have cilia -Ciliated type propelles mucous rectum), gallbladder, -Layer may contain (or reproductive cells) and excretory ducts mucus-secreting unicellular of some glands glands (goblet cells) -Ciliated type lines small bronchi, uterine tubes, and some parts of uterus Simple -Single layer of cells differing -Secrete substances, mainly -Ciliated type lines Pseudostratified in height mucous trachea and most of Columnar -Nuclei seen at different levels -Propulsion of mucus by ciliary upper respiratory -May contain mucus-secreting action tract cells and have cilia -Nonciliated type in male sperm-carrying ducts and ducts of large glands *There are two types of simple squamous epithelium based on location; Endothelium Downloaded by swim lowmess ([email protected])  ○ Lines inner surface of blood vessels, lymphatic vessels, and the heart ○ Derived from ectoderm and endoderm in the early embryo Mesothelium ○ Form serous membranes- surround pericardium, peritoneum, pleura, and internal reproductive organs (covers outer surface) ○ Derived from mesoderm ○ Two membrane system with fluid in between Types of Stratified Epithelium Type/Image Description Function Location Stratified Squamous -Thick, composed of several layers -Protects -Located in areas of high -Most widespread underlying tissue wear and tear -Basal cells are cuboidal or columnar and in areas subject to -Keratinized cells found metabolically active abrasion in skin and -surface cells are flattened (squamous) nonkeratinized found in -Keratinized type- surface cells are dead moist linings of mouth, and full of keratin. Basal cells are active esophagus and vagina in mitosis and produce superficial layer cells Stratified Cuboidal -Very rare -Found in some sweat -Typically only two layers thick and mammary glands Stratified Columnar -Very rare in the body -Transitional areas -only apical layer is columnar between two other types of epithelia -Small amounts found in pharynx, male urethra, and lining of some glandular ducts Transitional -Resembles both stratified squamous and -Stretches readily -Lines the ureters, stratified cuboidal -Permits stored bladder and part of the -Basal cells are cuboidal or columnar urine to distend urethra -Surface cells dome-shaped or squamous urinary organ like depending on the degree of organ stretch Glandular Epithelia Downloaded by swim lowmess ([email protected])  Gland-one or more cells that make and secrete an aqueous fluid called a secretion Classified by two factors ○ Site of product release Endocrine- internally secreting Exocrine- externally secreting ○ The relative number of cells forming the gland Unicellular (eg. goblet cells) or multicellular (eg. salivary) Formation of Multicellular Exocrine & Endocrine Glands Multicellular epithelial glands form by invagination (inward growth) of an epithelial sheet Exocrine glands retain the connecting cells, which form a duct that transports secretions to the epithelial surface Endocrine glands lose their ducts during development ○ Secrete hormones into the interstitial fluid which ten enter the blood Formation of Multicellular Endocrine & Exocrine Glands Multicellular epithelial glands form by invignation (inward growth) of an epithelial sheet ○ Exocrine glands retain connecting cells which form a duct that transports secretions into the epithelial surface ○ Endocrine glands lose their ducts during development. They secrete hormones into interstitial fluid which then enter the bloodstream Endocrine Glands Ductless Secretions are released into surrounding interstitial fluid which is then infused into the bloodstream Hormones- chemicals that travel through the lymph or blood to target organs that respond in a characteristic way Major glands of the endocrine system include; ○ Pineal gland, pituitary gland, pancreas, ovaries/testes, thyroid and parathyroid glands, hypothalamus, adrenal glands Exocrine Glands Secretions are released onto body surfaces (eg skin) or into body cavities More numerous than endocrine glands Secrete products into ducts Can be multicellular or unicellular Examples include mucus, sweat, oil, etc Unicellular Exocrine Glands ○ Only important ones are mucus cells and goblet cells ○ Found in epithelial linings of intestinal and respiratory tracts Downloaded by swim lowmess ([email protected])  ○ All produce mucin, a sugar protein that can dissolve in water to form mucus which is a slimy, protective coating Multicellular Exocrine Glands ○ Composed of duct and secretory unit ○ Usually surrounded by supportive connective tissue that supplies blood and innervation Connective tissue can form capsule around gland or extend into gland, dividing it into lobes ○ Classified by structure and modes of secretion as shown in the image below ○ Main modes of secretion Merocrine glands- secrete products via exocytosis Holocrine glands- secretory cell ruptures, releasing secretions and dead cell fragments Apocrine- accumulate products within, but only apex rupture (not sure if this type occurs in humans) Type 2- Connective Tissue Is the most abundant and widely distributed or primary tissues Major functions: binding and support, protection, insulation, storing reserve fuel and transporting substances 4 main classes; ○ Connective tissue proper, cartilage, bone, blood Overview of Classes of Connective Tissue (refer to ppt and textbook for chart) Downloaded by swim lowmess ([email protected]) Common Characteristics of Connective Tissue Three characteristics differentiate connective tissue from other types of primary tissue ○ Have common embryonic origin: mesenchyme ○ Have varying degrees of vascularization Eg; cartilage is avascular (lack of blood vessels) and bone is highly vascular (consists of vessels) ○ Cells are suspended/embedded in extracellular matrix (ECM) ECM supports cells so that they can bear weight, tension and abuse Structural Elements of Connective Tissue All connective tissues have 3 main elements ○ Ground substance, fiber and cells Ground substance and fiber together make up the ECM Composition and arrangement of these three elements vary in different types of connective tissues Ground Substance ○ Gel-like material that fills space between cells Is the medium through which solutes diffuse between blood capillaries and cells ○ Components Interstitial fluid Cell adhesion proteins Proteoglycans (sugar proteins) composed of protein core + large polysaccharides Water trapped in varying amounts, affecting the viscosity of ground substance Fibers ○ 3 types of fiber provide support Collagen Strongest, most abundant type Tough; provides high tensile strength Elastic Fibers Networks of long, thin elastin fibers Allow for stretch and recoil Reticular Short, fine, highly branched collagenous fibers Branching forms networks that offer more ‘give’ Cells ○ “-blast” cells Immature form of cell that secretes ground substance and ECM fibers Fibroblasts- found in connective tissue proper Chondroblasts- found in cartilage Osteoblasts- found in bone Downloaded by swim lowmess ([email protected])  Hematopoietic- stem cells in bone marrow ○ “-cyte” cells Mature, less active form of ‘-blast’ cell- is part of, and helps maintain the health of the ECM ○ Other cell types Fat cells- store nutrients White blood cells- tissue respond to injury (neutrophil, lymphocyte) Mast cells- initiate local inflammatory response against foreign microorganisms they detect (1st line of defence) Macrophages - phagocytic cells that eat dead cells; microorganisms that function in the immune system Refer to ‘Areolar connective tissue: A prototype’ slide in ppt for image of all components Types of Connective Tissue Proper Type/Image Description Function Location Loose Areolar -Most widely distributed -Universal packing material -Widely distributed connective tissue between other tissues under epithelia of the -Gel-like matrix containing -Wraps and cushions organs body all 3 fiber types and some -Plays an important role in -Eg: forms lamina white blood cells inflammation propria of mucous -Macrophages and fat cells are membranes, surrounds contained in spaces organs and capillaries -Loose fibers allow for increased ground substance, which can act as water reservoir Loose Adipose -Includes white (reserve) and -Shock absorption -Under the skin in brown fat (creates heat) -Insulation subcutaneous tissue -Similar to areolar tissue, but -Supports and protects organs -Around kidneys and greater nutrient storage -Provides reserve energy storage eyeballs -Cells are called adipocytes -Within abdomen -Sparse matrix -In breasts -Richly vascularized -Nucleus pushed to side by large fat droplets Loose Reticular -Loose network of reticular -Fibers form internal skeleton -Lymphoid organs fibers in ground substance (stroma) that supports other cell (lymph nodes, bone -Reticular (fibroblast) cells types including blood cells, mast marrow, spleen) lie on the fibers cells and macrophages Downloaded by swim lowmess ([email protected]) Dense Regular -Primarily thick, parallel -Very high tensile strength from -Tendons collagen fibers that are one direction -Ligaments slightly wavy -Attaches muscles to bones -Aponeuroses (flat -Major cell type is fibroblast tendon) -Few elastin fibers -Poorly vascularized Dense Irregular -Primarily irregularly -Withstands tension from many -Dermis of skin arranged collagen fibers directions -Fibrous capsules of -Forms sheets rather than -Provides structural strength organs or joints bundles -Submucosa of -Some elastin fibers digestive tract -Fibroblast is the main cell type Dense Elastic -Dense regular connective -Allows tissues to recoil after -Walls of large tissue stretching arteries -Contains a high proportion -Maintains pulsilate flow of blood -Certain ligaments of elastin fibers through arteries associated with -Aids passive recoil of lungs vertebral column following inspiration -Walls of bronchial tubes Cartilage Tough, yet flexible material that lacks nerve fibers Matrix secreted from chondroblasts (during growth) and chondrocytes (when adult) ○ Chondrocytes found in cavities called lacunae ○ 80% water, packed with collagen fibers and sugar proteins Is avascular ○ Receives nutrients and support from surrounding layer of dense, irregular CT Perichondrium provides to chondroblasts and chondrocytes Types of Connective Tissue Cartilage Tissue/Image Description Function Location Downloaded by swim lowmess ([email protected]) Cartilage Hyaline -Most abundant -Supports and reinforces -Forms most of -Amorphous (lacking structure), but -Serves as resilient cushion embryonic skeleton firm matrix -Resists compressive stress -Covers the ends of long -Appears as shiny bluish glass bones in joint cavities -Collagen fibers form imperceptible -Forms costal cartilages network of the ribs, nose, trachea -Chondrocytes lie in lacuna and larynx -Surrounded by perichondrium Cartilage Elastic -Similar to hyaline, but more elastic -Maintains the shape of a -Supports the external fibers in the matrix structure while allowing ear great flexibility -Epiglottis Fibrocartilage -Matrix similar to, but less firm than -Tensile strength allows it to -Intervertebral discs that in hyaline absorb compressive shock -Pubic symphysis -Thick collagen fibers predominate -Discs of knee joints -Strong Clinical Relevance of Cartilage Avascular cartilage loses ability to divide with age, so injuries heal slowly ○ Common in individuals with sports injuries Later in life, cartilage can calcify or ossify (become bony), causing chondrocytes to die Bone Type Description Function Location Bone -2 types of bone: compact bone and -Supports and protects -Bones spongy bone -Provides levers for the -Hard, calcified matrix containing muscles to act on many collagen fibers - Stores calcium, other -Osteocytes lie in lacunae minerals and fat -Very well vascularized -Marrow inside bones is -Calcium cannot be synthesized by site of blood cell formation the body. Bones are the source of (hematopoiesis) Ca -Bones supply extra calcium when needed Blood Downloaded by swim lowmess ([email protected])  Type Description Function Location Blood -Red and white blood -Transports respiratory -Contained within cells in a fluid matrix gasses, nutrients, blood vessels (plasma) water, wastes and other -Platelets substances -Derived from mesoderm Lecture 3- Plasma Membrane, Diffusion, Transport and Osmosis Chapter 3 Readings (Refer to ppt) Plasma Membrane Aka the cell membrane Acts as a barrier separating the intracellular fluid from the extracellular fluid Is a selective barrier- plays a role in cell activity by controlling what enters and leaves the cell Consists of membrane lipids that form a flexible lipid bilayer Plasma Membrane Lipids The plasma membrane consists of; ○ 75% phospholipids which consist of 2 parts; Phosphate heads- are polar and hydrophilic Fatty acid tails- are nonpolar and hydrophobic ○ 5% glycolipids Lipids with sugar groups attached to outer membrane surface ○ 20% cholesterol Increases membrane stability Component of lipid rafts Phospholipids Are amphipathic- contain both a hydrophilic and hydrophobic region In the digestive system, phospholipid containing bile salts help break up ingested lipids using amphipathic properties Plasma Membrane Proteins Specialized membrane proteins float through the fluid plasma membrane, resulting in constantly changing patterns ○ Referred to as fluid mosaic ○ Surface sugars form glycocalyx Membrane structures help hold cells together through cell junctions Functions Of The Plasma Membrane Downloaded by swim lowmess ([email protected])  Function Description Physical Barrier -Encloses the cell -Separates ICF from ECF Selective Permeability -Determines which substances enter or exit the cell Communication -Plasma membrane proteins interact with specific chemical protein messengers and relay messages to the cell interior outside-in and inside-out Cell Recognition -Cell surface carbohydrates allow cells to recognize each other Building Blocks of the Plasma Membrane Name Description Phospholipids -Form the basic structure of the membrane -Hydrophobic tales prevent water-soluble substances from crossing -Form a boundary Cholesterol -Stiffens membrane -Further decreases water solubility of the membrane -Typical 4 ring steroid structure Proteins -Determines what functions the membrane can perform -Many roles in communication, transport, signalling, joining cells, etc. -Proteins with different shapes have different functions Carbohydrates -Act as identity molecules -Allow for cell recognition during development so cells can sort themselves out into organs and tissues -Allow immune cells to recognize good and bad substances -Found only on the outer surface of the membrane -Together, all carbohydrates on outside of cell form a coating called the glycocalyx Membrane Proteins There are 2 types; ○ Integral membrane proteins ○ Peripheral membrane proteins Allow communication (signal transduction) with environment (bi-directional) Have specialized functions Downloaded by swim lowmess ([email protected])  Some float freely in the plane of the membrane while others are immobilized into cellular structures How do we know a protein is free to move in the plasma membrane? Fluid Mosaic Model Fluorescence recovery after photobleaching (FRAP) was used to help refine the fluid mosaic model Modification of Membrane Fluidity Membrane fluidity can be modified by a number of factors Cholesterol (up to 20%) and glycolipids (5%) and other specialized lipids can modify membrane fluidity Form lipid rafts- undergo endocytosis (refer to tb) Level of phospholipid saturation also have an effect Classes of Membrane Proteins Integral Membrane proteins ○ Firmly inserted into membrane ○ Most are transmembrane proteins ○ Have both hydrophobic and hydrophilic regions Hydrophobic areas interact with lipid tails Hydrophilic areas interact with water ○ Function as transport proteins (channels and carriers), enzymes or receptors Peripheral Membrane Proteins ○ Loosely attached to integral proteins or anchored to the membrane with covalently attached lipid groups ○ Can be on inner or outer part of the PM ○ Include filaments on intercellular surface which used for plasma membrane support ○ Function as; Enzymes Signal transduction (DEFINE) Scaffold proteins (DEFINE) Functions of Membrane Proteins Function Description Transport -A protien that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute Downloaded by swim lowmess ([email protected])  -Some transport proteins hydrolyze ATP as an energy source to actively pump substances across the membrane Receptors for Signal -A membrane protein exposed to the outside of the cell may have a Transduction binding site that fits the shape of a specific chemical messenger, suh as a hormone -When bound, the chemical messenger may cause a change in shape in the protein that initiates a chain of chemical reactions in the cell Enzymatic Activity -A membrane protein may be an enzyme with its active site exposed to substances in the adjacent solution -A group of several enzymes in a membrane may catalyze sequential steps of a metabolic pathway Cel-Cell Recognition -Some glycoproteins serve as identification tags that are specifically recognized by other cells -Important for cell-cell communication Attachment to -Elements of the cytoskeleton and the ECM may anchor to Cytoskeleton and ECM membrane proteins -Helps maintain cell shape, fixes the location of certain membrane proteins and plays a role in cell movement Cell-Cell Adhesion -membrane proteins of adjacent cells may be hooked together in various kinds of intercellular junctions -Some membrane proteins (cell adhesion molecules or CAMs) of this group provide temporary binding sites that guide cell migration and other cell-cell interactions Glycolax Consists of sugars (carbohydrates) sticking out of the cell surface ○ Some sugars are attached to lipids (glycolipids) and some to proteins (glycoproteins) Every cell has different patterns of this ‘sugar coating’ ○ Functions as specific biological markers for cell to cell recognition ○ Allows immune system to recognize self vs. nonself Cell Junctions Are specialized areas of the plasma membrane There are three types ○ Gap Junctions Communicating junctions Allow ions and small molecules to pass from cell to cell Particularly important in heart cells and embryonic cells Eg: Channels formed by connexons Found in epithelial cells and some nerve cells Downloaded by swim lowmess ([email protected])  ○ Desosomes Anchoring junctions Bind adjacent cells together like molecular velcro Help keep cells from tearing apart Eg: Linker proteins (cadherins) ○ Tight junctions Impermeable junctions Form continuous seals around the cell Prevent molecules from passing between cells Eg: Interlocking junction proteins Gap Junctions Transmembrane proteins (connexons) form tunnels or gaps between cells that allow small molecules to pass from cell to cell Used to spread ions, simple sugars or other small molecules between cells Allows electrical signals to be passed quickly from cell to cell ○ Mostly in cardiac and smooth muscle cells, but sometimes in neurons Transport of Substances Across the PM Many substances constantly move across the plasma membrane ○ Some molecules pass through easily and some do not The plasma membrane is selectively permeable, allowing only certain molecules to pass through Two essential ways substances can cross the PM; ○ Active Transport: energy (ATP) is required ○ Passive Transport: No energy is required Passive Membrane Transport Requires no energy input Three types of passive diffusion: ○ Simple diffusion ○ Facilitated diffusion ○ Osmosis All types involve diffusion- the natural movement of molecules from areas of high concentration to areas of low concentration ○ Also referred to as moving down a concentration gradient How Does Diffusion Work? All molecules have random, high-speed movement due to their intrinsic kinetic energy Movement results in collisions between molecules Downloaded by swim lowmess ([email protected])  Molecules in higher concentration areas collide more, resulting in molecules being scattered to lower concentration areas- called diffusion Factors That Affect Diffusion The speed of diffusion is affected by 3 factors ○ Concentration The greater the difference of concentration between the two areas, the faster the diffusion occurs ○ Molecular Size Smaller molecules diffuse faster ○ Temperature Higher temperatures increase kinetic energy which results in faster diffusion Equilibrium is reached when there is no net movement of molecules in one direction Diffusion Across the Plasma Membrane Molecules have a natural drive to diffuse down concentration gradients that exist between extracellular and intracellular areas Nonpolar, hydrophobic lipid core of the PM prevents the diffusion of some substances and creates concentration gradients by acting as a selectively permeable barrier Molecules that are able to diffuse passively through the membrane include: ○ Lipid-soluble and nonpolar substances ○ Very small molecules that can pass through membrane or membrane channels ○ Referred to as simple diffusion Flux- movement of molecules in any certain direction Simple Diffusion Nonpolar lipid-soluble (hydrophobic) substances diffuse directly through phospholipid bilayer ○ Eg: oxygen, carbon dioxide, steroid hormones, fatty acids Small amounts of very small polar substances, such as water, can also pass through Facilitated Diffusion Larger, non-lipid soluble or polar molecules can cross membrane but only with the support of carrier molecules ○ This is facilitated diffusion There are 2 types: ○ Carrier- mediated ○ Channel- mediated Use different types of integral membrane proteins Impact different properties to transport Carrier-Mediated Facilitated Diffusion Downloaded by swim lowmess ([email protected])  Certain hydrophobic molecules are transported passively down their concentration gradient by carriers (transmembrane proteins) Each carrier transports specific substances Binding of molecule causes carrier to envelope and change shape (conformational change) that results in the molecule being moved across the membrane The rate of transport of a substance across a membrane depends on three factors ○ Find in Textbook Channel Mediated Facilitated Diffusion Some integral membrane proteins form channels that allow ions to diffuse across the membrane Ion channels show selectivity for particular types of ions based on channel diameter, charged residue lining pore, water of hydration Osmosis Is a special name for the net movement of water across a selectively permeable membrane Water diffuses across plasma membranes ○ Some through lipid bilayer (some sneak past ist hydrophobic barriers) ○ Mostly through specific water channels called aquaporins (AQP’s) Prevent the passage of ions and other solutes. Only water can go through Impermeable to charged species Flow occurs when the water concentration is different on the two sides of the membrane Water is a polar molecule but it rapidly diffuses across the plasma membrane of most cells A liter of pure water is 55.5 M (moles/mass) The addition of solute lowers the water concentration ○ This depends on the number of solute particles, not the chemical nature of the solute Osmolarity Osmolarity: measures the total number of solute particles in a solution ○ Water concentration varies with number of solute particles- solute particles displace water molecules When solute concentration goes up, water concentration goes down and vise versa Osmolarity= molarity x the number of particles that a substance forms in water ○ 1 M solution of glucose is 1 Osm ○ 1 M solution NaCl ionizes to Na+ and Cl- (2 particles) is 2 Osm (osmolar or osmol/L) ○ 1 M solution of MgCl2 is 3 Osm ○ A 3 Osm solution may have 1 M glucose and 2 M NaCl Water moves by osmosis from areas of high solute (high water) to areas of low solute (low water) concentration ICF and ECF is approximately 300 mOsm Downloaded by swim lowmess ([email protected]) Osmotic Pressure When a solution containing solutes separated from pure water by a semi-permeable membrane (permeable to water but not solutes), the pressure that must be applied to the solution to prevent the net flow of water into it is called the osmotic pressure The greater the osmolarity of a solution, the greater its osmotic pressure and the lower its water concentration Membrane Permeability Influences Diffusion and Osmosis When solutions of different osmolarities are separated by a membrane permeable to all molecules, diffusion of solutes and osmosis of water occur ○ Cross membrane until equilibrium of solutes and water is reached At equilibrium: Same concentration of solutes and water molecules on both sides, with equal volume on both sides When solutions of different osmolarities are separated by a membrane that is only permeable to water, only osmosis (not diffusion) will occur until equilibrium is reached Water will have net movement across membrane until its concentration (or osmolarity) is the same on both sides Results in volume changes on both sides ○ Low solutes side volume decreases ○ High solute side volume increases ○ Only molecules that cannot cross the PM cause volume changes Osmosis Movement of water involves pressures: ○ Hydrostatic pressure: outward pressure exerted on cell side of the membrane caused by increases in volume of cell due to osmosis Also referred to as ‘back pressure’ ○ Osmotic pressure: inward pressure due to the tendency of water to be pulled into a cell with higher osmolarities The more solutes inside a cell the bigger the pull on water to enter, resulting in higher osmotic pressures inside the cell When hydrostatic pressure equals osmotic pressure, no further net movement of water occurs ○ Water trying to get out equals water trying to get in Plant cells are surrounded by strong cell walls that act to limit hydrostatic pressure levels which in turn limit osmotic pressure ○ Plant cells can only fill with so much water then stop Animal cells don’t have cell walls, therefore they cannot limit hydrostatic and osmotic pressures ○ Animal cells will burst if too much water is taken in Water can also leave a cell, causing it to shrink Changes in cell volume can disrupt cell function Downloaded by swim lowmess ([email protected]) Extracellular Osmolarity and Cell Volume Na+, Cl-, K+ Will not be tested on the last point Tonicity Refers to the ability of a solution to change the shape or tone of cells by altering the cells internal water volume ○ Isotonic solution has the same osmolarity of non-penetrating solutes as inside the cell, so volume remains unchanged ○ Hypertonic solution has a higher osmolarity non-penetrating solutes than inside the cell, so water flows out of the cell, resulting in cell shrinking (crenation) ○ Hypotonic solution has a lower osmolarity non-penetrating solutes than inside the cell, so water flows into the cell, resulting in cell swelling Can lead to cell bursting (lysis) Lecture 4- Membrane Transport and Resting Membrane Potential Carrier-Mediated Transport Integral membrane proteins move via conformational changes Three factors determine the magnitude of solute flux through a mediated transport system: ○ The extent to which the binding sites are ‘saturated’ (maximally occupied) ○ The number of transporters in the membrane ○ The rate at which the conformational change occurs There are many types of transporters that are specific for a substance or class of substances Transpor fewer molecules per unit time than ion channels ○ Saturable binding There are two types of mediated transport: ○ Facilitated diffusion ○ Active transport Facilitated Diffusion and Active Transport Facilitated diffusion- net flux proceeds across a membrane from higher to lower concentration Simple diffusion- flux limited only by the concentration gradients In carrier-mediated transport, flux depends on the number of available characters Active transport- net movement of solute from a lower concentration to a higher concentration requires continuous input of energy from ATP There are two means of coupling ATP to active transport: ○ The direct use of ATP in primary active transport ○ The use of an electrochemical gradient to drive secondary active transport Downloaded by swim lowmess ([email protected]) Primary Active Transport- Na+/K+ ATPase ATP hydrolysis provides the energy for primary active transport Transporters are ATPases- enzymes that hydrolyze ATP (break down using water) ○ Eg: Na+/K+ ATPase pump How it works: ○ The transporter (with bound ATP) binds 3 Na+ on inside of cell (low affinity for K+) ○ ATPase activated. Autophosphorylation. ○ Conformational change and release of Na+ to outside ○ Increased affinity for K+ allows two K+ to bind ○ Dephosphorylation and return to original conformation. Release of K+ to inside. Each ATP hydrolysis moves 3 Na+ outside and 2 K+ inside the cell A Chemical and Electrical Gradient The pumping activity of the Na+/K+ ATPase establishes and maintains the characteristic distributions of K+ and Na+ The unequal distribution of ions creates an electrical potential across the PM ○ Can be used for transport and/or signalling Thus the Na+/K+ ATPase establishes an electrochemical gradient that: ○ Can be used to do work (eg: transport of other solutes) ○ Is the basis for electrical impulses in neurons Na+/K+ ATPase pump uses 10-40% of ATP in cell under resting conditions to maintain gradient Secondary Active Transport Uses the stored energy of an electrochemical gradient to move both an ion and second solute across a membrane ○ The creation of the electrochemical gradient depends on the primary active transporter Secondary active transport- movement of ion down its electrochemical gradient coupled to the transport of another molecule ○ These transporters have binding sites for an ion (usually Na+) and the co-transported molecule Symporters and Antiporters In secondary active transport, the movement of Na+ is always downhill (from high to low) Co-transport (symport): the ion and second solute move across the membrane in the same direction Countertransport (antiport): the ion and second solute move in opposite direction Vesicular Transport Involves the transport of large molecules, particles, and fluids across the membranous sacs called vesicles Required cellular energy (usually ATP) Downloaded by swim lowmess ([email protected])  Vesicular transport processes include; ○ Endocytosis: transport into cells. Are 3 different types: phagocytosis, pinocytosis and receptor-mediated endocytosis ○ Exocytosis: transport out of cell ○ Transcytosis: transport into, across, then out of the cell ○ Vesicular trafficking: transport from one area or organelle to another Endocytosis Involves formation of protein-coated vesicles (bend membrane) Usually involves receptors: therefore can be a very selective process ○ Substance being internalized must be able to bind to its unique receptor Once a vesicle is pulled inside the cell, it may: ○ Fuse with lysosome OR ○ Undergo transcytosis Some pathogens are capable of hijacking receptors for transport into cell (some take advantage of acidic lysosome environment) Phagocytosis Type of endocytosis that is referred to as ‘cell eating’ Membrane projections called pseudopods form and flow around solid particles that are being engulfed, forming a vesicle that is pulled into a cell ○ Formed vesicle is called a phagosome ○ Phagocytosis is used by macrophages and other white blood cells The phagosome combines with a lysosome and its contents are digested The vesicle has receptors capable of binding to microorganisms or solid particles Pinocytosis Fluid phase endocytosis or ‘cell drinking’ ○ Plasma membrane infolds, bringing extracellular fluid and dissolved solutes inside the cell ○ Fuses with endosome Used by some cells to sample environment Is the main way in which nutrient absorption occurs in the small intestine Membrane components are recycled back into membrane No receptors used, so it is non-specific Receptor-Mediated Endocytosis Involves endocytosis and transcytosis of specific molecules Substances bind to specific receptor proteins, enabling the cell to ingest and concentrate specific substances in protein coated vesicles Downloaded by swim lowmess ([email protected])  Many cells have receptors embedded in clathrin-coated pits which will be internalized along with the specific molecule bond ○ Eg: enzymes, low density lipoproteins (LDL), iron and insulin ○ Contain viruses, diphtheria, and cholera toxins may also be taken into the cell this way Substances may be released inside cell or digested in a lysosome Caveolae have smaller pits and different protein coat from clarathin, but still capture specific molecules and sometimes use transcytosis Associated with lipid rafts (cholesterol and other special lipids) Overview of Endocytosis By Protein-Coated Pits 1. Coated pit ingestes substance 2. Protein coated vesicle detaches from plasma membrane 3. Coat proteins are recycled to PM 4. Uncoated vesicle fuses with sorting vesicle called an endosome 5. Transport vesicle containing membrane components moves to the plasma membrane for recycling 6. Fused vesicle may: a. Fuse with lysosomes for digestion of its contents b. Deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis) Exocytosis Process by which material is ejected from the cell ○ Usually activated by cell-surface signals or changes in membrane Substances being ejected in secretory vesicles Protein on vesicle called v-SNARE finds and hooks up to target t-SNARE proteins on membrane Eg: hormones, neurotransmitters, mucus, cellular wastes Overview of Exocytosis 1. The membrane bound vesicle migrates to the plasma membrane 2. Proteins at the vesicle surface (v-SNARES) bind with t-SNARES (plasma membrane proteins) 3. The vesicle and plasma membrane fuse and a pore opens up 4. Vesicle contents are released to the cell exterior Cell Environment Interactions Cells interact with the environment by responding directly to other cells, or indirectly to extracellular chemicals Interactions always involve glycolax ○ Cell adhesion molecules (CAMs) ○ Plasma membrane receptors Downloaded by swim lowmess ([email protected]) Cell Adhesion Molecules (CAMs) Every cell has thousands of sticky glycoprotein CAMs projecting from membrane Functions: ○ Anchor cell to extracellular matrix or to each other ○ Assist in the movement of cells past one another ○ Attract WBCs to injured or infected areas ○ Stimulate synthesis or degradation of adhesive membrane junctions (eg: tight junctions) ○ Transmit intracellular signals to direct cell migration, proliferation, and specialization Plasma Membrane Receptors Membrane receptor proteins serve as binding sites for several chemical signals Contact signalling: cells that touch, recognize each other by each cell’s unique surface membrane receptors ○ Used in normal development and immunity Signal Transduction: interaction between receptor and ligands (chemical messengers) that cause changes in cellular activity ○ Ligands can be small molecules or proteins ○ In some cells, binding triggers enzyme activation; in others, it opens chemically gated ion channels causing changes in excitability Eg of ligands: neurotransmitters, hormones and paracrines ○ Some ligands can cause different responses in different cells depending on chemical pathway that the receptor is part of ○ When ligand binds, receptor protein changes shape (conformation) and becomes activated ○ Some activated receptors become enzymes; others act directly to open or close ion gates, causing changes in excitability ○ All transduce signals across the PM G Protein-Coupled Receptors (GPCRs) Activated G protein-coupled receptors indirectly cause cellular changes by attracting G proteins, which in turn can affect ion channels, activate other enzymes or cause release of internal second messenger chemicals such as cyclic AMP or calcium GPCR Superfamily: >800 7 TM - receptors participate in diverse physiological and pathological functions ○ 36% of marketed pharmaceuticals target human GPCRs Orphan GPCRs: ‘Endogenous’ ligands of more than 140 GPCRs unknown, leaving the natural functions of those GPCRs in doubt, a great source of drug targets Overview of G Protein-Coupled Receptors (GPCRs) Downloaded by swim lowmess ([email protected])  1. Ligand (1st messenger) binds to the receptor causing it to change shape and activate. 2. Activated receptor binds to a G protein and activates it. G protein changes shape, causing it to release GDP and bind GTP 3. Activated G protein activates (or inactivates) an effector protein by causing its shape to change 4. Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (common second messengers: cyclic AMP and C^21) 5. Second messengers activate other enzymes or ion channels. Cyclic AMP usually activates protein kinase enzymes 6. Kinase enzymes activate other enzymes. They transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various metabolic reactions and structural changes in the cell. Lecture 5- Fundamentals Of The Nervous System Neurons Neurons (nerve cells) are highly specialized cells that are the basic functional units of the nervous system Special characteristics: ○ Excitable cells (conduct electrical impulses) ○ Extreme longevity (lasts a person’s lifetime) ○ Postmitotic (don't undergo mitosis) with fe exceptions ○ Higher metabolic rate: require continuous supply of oxygen and glucose All neurons have a cell body and one or more slender processes Neuron Cell Body Also called the perikaryon or soma ○ 5-140 um diameter Biosynthetic center of neuron ○ Synthesizes proteins, membranes, chemicals ○ Rough ER (chromatophilic substance or nissl bodies) Contains spherical nucleus with nucleolus Neurons in the SN contain a pigment related to melanin PM is usually part of receptive region that receives input from other neurons Most neuron bodies are located in the CNS but some are in PNS ○ Nuclei: clusters of neuron cell bodies in the CNS (gray matter) ○ Ganglia: clusters of neuron cell bodies in PNS Neuron Processes Arm like processes that extend from cell body ○ CNS contains both neuron cell bodies and their processes Downloaded by swim lowmess ([email protected])  ○ PNS contains chiefly neuron processes Tracts (usually white matter) ○ Bundles of neuron processes in CNS Nerves ○ Bundles of neuron processes in PNS Two types of processes: ○ Dendrites ○ Axon Dendrites Neurons can contain 100s of these short tapering, diffusely branched processes Same organelles as in stroma Receptive (input) region of neuron Convey incoming messages toward cell body as graded potentials (short distance signals) In many brain areas, finer dendrites are highly specialized to collect information ○ Contain dendritic spines, appendages with bulbous or spiky ends ○ Shape modified by activity- basis for learning and memory Axon Structure Each neuron has a single axon that starts a cone shaped area close to the soma called axon hillock Axons can be short or extremely long (>1 meter)- called nerve fibers Can have occasional branches (at 90 degrees) called axon collaterals Axons branch profusely at their end (terminus)- as many as 10,000 terminal branches Distal endings are called axon terminals or terminal boutons Axon Function Axon is the conducting region of neuron (conducts information away from the cell body) Generates nerve impulses and transmits them along axolemma (axon cell membrane) to axon terminal, a region that secretes neurotransmitters, which are released into the extracellular space ○ Can excite or inhibit neurons it contacts Communicates with many different neurons at the same time Axons rely on cell bodies to renew proteins and membranes Quickly decay of cut or damaged (PNS vs CNS) Axonal Transport Axons have efficient internal transport mechanisms Molecules and organelles are moved along axons by motor proteins and cytoskeletal elements ○ Anterograde: away from the cell body Downloaded by swim lowmess ([email protected])  Eg: mitochondria, cytoskeletal elements, membrane components, enzymes, synapses-specific proteins, neurotransmitters, certain mRNA’s ○ Retrograde: towards cell body Eg: organelles to be degraded, signalling molecules, viruses and bacterial toxins Peripheral Myelination Formed by schwann cells ○ Wraps around axon ○ One cell forms one segment of the myelin sheath Outer collar of perinuclear cytoplasm: peripheral bulge containing nucleus and most of cytoplasm Plasma membranes have less proteins No channels or carriers, so good electrical insulators Cell adhesion molecules (CAMs) bind to adjacent myelin membranes Myelin Sheath Gaps ○ Gaps between adjacent schwann cells ○ Sites where axon collaterals can emerge ○ Also called nodes of ranvier Non-Myelinated Fibers ○ Thin fibers not wrapped in myelin ○ Surrounded by schwann cells but no coiling ○ One cell may surround 15 different fibers Central Myelination Myelin sheaths in the CNS ○ Formed by processes of oligodendrocytes, not whole cells ○ Each cell can wrap up to 60 axons at once ○ Also forms nodes of ranvier ○ No outer collar of perinuclear cytoplasm ○ Speeds up transmission of action potentials ○ Thinnest fibers are unmyelinated, but covered by long extensions of adjacent neuroglia ○ White matter: regions of the brain and spinal cord with dense collection of myelinated fibers Usually fiber tracts ○ Gray matter: mostly neuron cell bodies and unmyelinated fibers Membrane Potential in Neurons Like all cells, neurons have a resting membrane potential- charge difference across PM Neurons can rapidly change the membrane potential due to the presence of additional ion channels Neurons (and muscle cells) are excitable cells as they can conduct electrical potentials Downloaded by swim lowmess ([email protected]) Basic Principles of Electricity Opposite charges attract each other and will move towards each other if not separated by some barrier Separate charges have the ability to do work- called electrical potential Difference in charge between two points is called potential difference (or just potential) ○ Measured in volts (v) Movement of electrical charge: current Ohm’s Law: Current is proportional to the potential difference and inversely proportional to the resistance I=V/R Insulator: a substance with high electrical resistance Conductor: substances with low electrical resistance Summary: Establishing The RMP The Na+/K+ ATPase establishes a concentration gradient and generates a small negative potential ○ Pump uses up to 40% of the ATP produced but the cell Greater net movement of K+ than Na+ makes the membrane potential more negative on the inside At a steady state, ion fluxes through the channels and activity of the pump balance each other Distribution of Ions in a Nerve Cell Na+, K+ and Cl- are present in the highest concentration and membrane permeability to each is independently determined Na+ and K+ play the most important role in generating the resting membrane potential but Cl- is a factor in some neurons Remember: Na+ Cl- out, K+ in The resting membrane potential is established and determined mainly by Na+/K+ ATPase activity Cl- is NOT on Exam Equilibrium Potential The magnitude of the membrane potential depends mainly on two factors ○ (Ion) differences out vs in ○ Membrane permeability to different ions (# of open channels for each ion) A membrane that is permeable only to K+ (refer to this slide in lecture 5 ppt) The membrane potential at which the flux due to concentration difference becomes equal in magnitude but opposite in direction is called the equilibrium potential for that type of ion Consider a membrane permeable only to Na+ (refer to this slide in lecture 5 ppt) The Nernst Equation Downloaded by swim lowmess ([email protected])  The Nernst equation describes the equilibrium potential for any ion species ○ The electrical potential necessary to balance a given ionic concentration gradient across a membrane so that the net flux on that ion is zero Eion= 61/Z log (Co/Ci) ○ Eion = equilibrium potential in mV ○ Ci = intracellular ion concentration ○ Co = extracellular ion concentration ○ Z = valence of the ion ○ 61 is a constant that takes into account the universal gas constant, the temperature, and the Faraday electrical constant When there is a bigger number over a smaller number, the log will be positive and when there is a smaller number over a bigger number, the log will be negative ○ ENa= 61/1 log (145/15) = +60 mV ○ EK= 61/1 log (5/15) = -90 mV At typical concentrations (table 6.2), Na+ flux through open channels will drive the membrane potential towards +60 mV while K+ flux will bring it towards -90 mV ○ In an actual nerve at rest, there are many more open K+ channels than Na+ channels; chloride permeability generally falls in between ○ PK= 1, PNa= 0.04, PCl= 0.45 Forces Influencing Na+ and K+ At Resting Membrane Potential At a resting membrane potential of -70 mV, both the concentration gradient and electrical potential favour inward movement of Na+ while K+ concentration gradient opposes the electrical potential The greater permeability and movement of K+ maintains the resting membrane potential at a value near EK Resting Membrane Potential Electrical potential energy produced is by the separation of oppositely charged particles across the plasma membrane in all cells ○ The difference in electrical charge between two points is referred to as voltage A voltmeter can measure the potential difference across the membrane of a resting neuron of -70 mv Resting membrane voltages range from -50 to -100 mV in different cells ○ The membrane is said to be polarized All cells under resting conditions have a potential difference with the inside being more negative ○ This is called the resting membrane potential ECF has a voltage of zero If the potential across the membrane is 70 mV and the ICF has excess negative charge, then membrane potential is -70 mV Downloaded by swim lowmess ([email protected])  Membrane potential is determined by two factors: ○ Differences in ionic composition of ICF and ECF ○ Differences in plasma membrane permeability to each ion Charge Separation Across Plasma Membrane Voltage occurs only at the membrane surface ○ Rest of cell and extracellular fluid are neutral There is a tiny excess of negative ions along inner surface of PM and positive ions around the outside Excess charges collect at the plasma membrane and are attracted to each other The actual number of charges that are separated is small compared to the total number of charges in the cell Only a very thin shell of charge difference is needed to establish a membrane potential Resting Membrane Potential Depends on: ○ Differences in K+ and Na+ concentrations inside and outside cells ○ Differences in permeability of the PM to these ions Energy is required to keep opposite charges separated across a membrane Leak Channels Generate the Resting Potential Leak Channels: (not ligand-gated) are integral membrane proteins that are selective ion channels- some are always open In a neuron at rest, there are many more open K+ leak channels than Na+ leak channels So PM is 25 times more permeable to K+ than Na+ This brings RMP closer to the K+ equilibrium potential therefore , the RMP depends mostly on K+ ○ Na+/K+ ATPase maintains resting membrane potential by maintaining concentration gradients Forces Influencing Na+ and K+ At Rest At a resting membrane potential of -70 mv, both the concentration gradient and electrical potential favour inward movement of Na+, while the K+ concentration gradient opposes the electrical potential The greater permeability and movement of K+ maintains the resting potential at a value near EK Types of Ion Gated Channels Chemically Gated (ligand gated) Channels ○ Open only with binding of specific chemical (eg: neurotransmitter) Voltage Gated Channels ○ Open and close in response to changes in membrane potential Downloaded by swim lowmess ([email protected])  Mechanically Gated Channels ○ Open and close in response to physical deformation of receptors, as in sensory receptors When gated channels open, ions diffuse quickly: ○ Along chemical concentration gradients from high to low concentration ○ Along electrical gradients, towards opposite electrical charge Changes in Membrane Potential Membrane potential changes when: ○ Concentrations of ions across membrane change ○ Membrane permeability to ions change (opening of channels) Changes produce two types of signals ○ Graded potentials Incoming signals operating over short distance ○ Action potentials Long- distance signals of axons Changes in membrane potential are used as signals to receive, integrate and send information Terms describing membrane potential changes relative to RMP: ○ Depolarization: a decrease in membrane potential (moves towards zero and above) Inside of membrane becomes less negative than RMP Probability of producing impulses increases ○ Hyperpolarization: increase in membrane potential (away from zero) Inside of a membrane becomes more negative than RMP Probability of producing impulse decreases Graded Potentials Short lived, localized changes in membrane potential ○ The stronger the stimulus, the more voltage changes and the further current flows Triggered by stimulus that opens gated ion channels ○ Results in depolarization or hyperpolarization Named according to location and function ○ Receptor potential (generator potential): graded potentials in receptors of sensory neurons ○ Postsynaptic potential: neuron graded potential Once gated ion channel opens, depolarization spreads from one area of membrane to the next Current flows but dissipates quickly and decays ○ Graded potentials are signals only over short distances Action Potentials Principle way neurons send signals ○ Means of long distance neural communication Only occur in muscle cells and axons of neurons (excitable cells) Downloaded by swim lowmess ([email protected])  ○ Aka nerve impulse Involves opening of specific voltage-gated channels Brief reversal of membrane potential with a change in voltage of 100 mV Don’t decay with distance like graded potentials Voltage-Gated Channels An action potential (AP) results from changes in ion permeability due to the function of voltage-gated Na+ and K+ channels APs are generally very rapid (can be a few milliseconds) and can have frequencies of several hundred/second Voltage-gated channels give the membrane the ability to generate and propagate APs Action Potential Mechanism Absolute refractory period ○ The period of time during which a second action potential ABSOLUTELY cannot be initiated, no matter how large the applied stimulus is Relative refractory period ○ the period shortly after the firing of a nerve fiber when partial repolarization has occurred and a greater than normal stimulus can stimulate a second response Refer to ppt 5 and textbook Action Potentials are All or Nothing APs occur in excitable membranes with voltage gated sodium channels (VGSCs) These channels open as the membrane depolarizes, causing a positive feedback opening of more VGSCs and moving the membrane potential towards ENa Local anesthetics (procaine and lidocaine) block VGSCs The number of ions that cross the membrane during an AP is extremely small compared to the total number of ions in the cell, producing only small changes in the IC ion concentrations Threshold Potential Depolarization triggers an AP only when the membrane potential exceeds a threshold potential (55 mV) Regardless of the size of the initial stimulus, if the membrane reaches threshold, the APs generated are all the same size APs propagate without any change in size from one site to another along a membrane ○ Don’t decay like graded potentials Because it its ‘all or none’, a single AP cannot convey the information about the magnitude of the initial stimulus How is information encoded in the nervous system? Action Potential Propagation Downloaded by swim lowmess ([email protected])  The (local) current entering during an AP is sufficient to easily depolarize the adjacent emembrane to the threshold potential The propagation of the AP from the dendrites to the axon terminal is typically one way because the absolute refractory period follows along the wake of the moving AP The speed of propagation depends on fiber diameter (why?) and whether or not the fiber is myelinated Saltatory Conduction In myelinated nerve fibers, APs undergo saltatory conduction Action potentials jump from one node of ranvier to the next as they propagate along a myelinated axon Multiple Sclerosis- Myelin breakdown Lecture 6- Synapses The Synapse Nervous system works because information flows from neuron to neuron Neurons are functionally connected by synapses- junctions that mediate information transfer ○ From one neuron to another neuron ○ OR from one neuron to an effector cell Presynaptic neuron: neuron conducting impulses towards synapse (sends information) Postsynaptic neuron: neuron transmitting electrical signal away from synapse (receives information) ○ In PNS may be a neuron, muscle cell or gland cell Most neurons function as both Synaptic Connections Axodendritic: between axon terminals of one neuron and dendrites of another Axosomatic: between axon terminals of one neuron and soma (cell body) of others Less common connections; ○ Axoaxonic: axon to axon ○ Dendrodendritic: dendrite to dendrite ○ Somatodendritic: dendrite to soma Two main types of synapses ○ Chemical synapse ○ Electrical synapse Chemical Synapses Is the most common type Specialized for release and reception of chemical neurotransmitters Typically composed of two parts: Downloaded by swim lowmess ([email protected])  ○ Axon terminal of presynaptic neuron: contains synaptic vesicles filled with neurotransmitter ○ Receptor region on postsynaptic neuron’s membrane: receives neurotransmitter Usually on dendrite or cell body ○ Two parts separated by fluid-filled synaptic cleft Electrical impulse changed to chemical across synapse, then back into electrical Transmission across synaptic cleft ○ Synaptic cleft prevents nerve impulses from directly passing from one neuron to the next ○ Chemical event (as opposed to an electrical one) ○ Depends on release, diffusion, and receptor binding of neurotransmitters ○ Ensures unidirectional communication between neurons Events at Chemical Synapses 1. AP arrives at presynaptic terminal 2. Voltage-gated Ca2+ channels open in response to depolarization. 3. Ca2+ influx causes synaptic vesicles to fuse with PM and release neurotransmitter (NT) by exocytosis. 4. NT diffuses across the synaptic cleft and binds to its specific postsynaptic receptor(s) 5. Neurotransmitter binding opens ion channels resulting in a graded potential 6. NT effects are terminated by several mechanisms a. Reuptake by transporters b. Diffusion away from synapse c. Enzymatic degradation Synaptic Delay Time needed for neurotransmitter to be released, diffuse across the synapse, and bind to receptors ○ Can take anywhere from 0.3 to 5.0 ms Rate-limiting step of neural transmission Transmission of AP down axon can be very quick, but synapse slows transmission to postsynaptic neuron down significantly Not noticeable, because these are still very fast Electrical Synapses Less common than chemical synapses ○ Don’t have delays like chemical synapses Neurons are electrically coupled ○ Joined by gap junctions that connect the cytoplasm of adjacent neurons ○ Communication is very rapid and may be unidirectional or bidirectional Downloaded by swim lowmess ([email protected])  ○ Found in some brain regions responsible for eye movements or hippocampus in areas involved in emotions and memory ○ More abundant in embryonic nervous tissue, heart and smooth muscle Postsynaptic Potentials Neurotransmitter receptors cause graded potentials that vary in strength based on: ○ Amount of neurotransmitter released ○ Time neurotransmitter stays bound to its receptor Depending on the effect of chemical synapse, there are two types of postsynaptic potentials ○ EPSP: excitatory postsynaptic potentials ○ IPSP: inhibitory postsynaptic potentials Excitatory Synapses and EPSPs Neurotransmitter binding opens chemically gated channels (usually a non-selective cation channel) Allows simultaneous flow of Na+ and K+ in opposite directions Na+ influx greater than K+ efflux, resulting in a depolarizing graded potential called excitatory postsynaptic potential (EPSP) EPSPs trigger AP at axon hillock if the membrane potential reaches threshold ○ This triggers opening of voltage-gated Na+ channels Glutamate is the major excitatory NT in the CNS Occur on dendritic spines Inhibitory Synapses and IPSPs Neurotransmitter binding to receptor opens chemically gated channels that allow influx/efflux of ions that cause a hyperpolarization. ○ e.g. K+ channel or Cl- channel Moves the membrane potential further away (more negative) from threshold to fire an AP ○ Called in inhibitory postsynaptic potential (IPSP) Glycine and gamma-aminobutyric acid (GABA) are inhibitory neurotransmitters in the CNS Integration and Modification of Synaptic Events Postsynaptic ○ Often, a single EPSP cannot induce an AP, but EPSPs can summate (add together) to influence postsynaptic neuron IPSPs can also summate ○ Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons Only if EPSPs predominate and bring to threshold will an AP be generated Downloaded by swim lowmess ([email protected])  There are two types: Temporal summation ○ One or more presynaptic neurons transmit impulses in rapid-fire order ○ First impulse produces EPSP, and before it can dissipate another EPSP is triggered, adding on top of first impulse Spatial summation ○ Postsynaptic neuron is stimulated by a large number of terminals simultaneously ○ Many receptors are activated, each producing EPSPs, which can then add together Activity Dependant Synaptic Potentiation Repeated use of synapse increases ability of presynaptic neuron to excite postsynaptic neuron Presynaptic changes ○ Ca2+ concentration increases in presynaptic terminal - release of more neurotransmitter - more EPSPs in postsynaptic neuron Postsynaptic changes ○ Potentiation can cause Ca2+ voltage-gated channels to open in postsynaptic neuron. Ca2+ activates kinases, leading to more effective response to subsequent stimuli ○ NMDA receptors (Mg2+ block removed by strong depolarization) ○ Long-term potentiation involved in learning and memory Comparison of Graded and Action Potentials Refer to ANP Reference Charts Developmental Aspects of Neurons Nervous system originates from neural tube and neural crest (ectoderm) ○ The neural tube becomes CNS Neuroepithelial cells of neural tube proliferate into number of cells needed for development Neuroblasts ○ Become amitotic and migrate to final positions ○ Sprout axons to connect with targets and become neurons Growth cone: structure at tip of axon that allows it to interact with its environment via: ○ Cell surface adhesion proteins (laminin, integrin, and nerve cell adhesion molecules, or N-CAMs), which provide anchor points ○ Neurotrophins that attract or repel the growth cone ○ Nerve growth factor (NGF), which keeps neuroblast alive ○ Filopodia are growth cone processes that follow signals toward target Developmental Aspects of Neurons Downloaded by swim lowmess ([email protected])  Once axon finds its target, it then must find the right place to form synapse (Roger Sperry - Chemo