Animal Physiology Lecture Notes - 2024 PDF

20373-X: ZOOLOGY 120 ANIMAL PHYSIOLOGY | LECTURE FOUNDATIONS OF PHYSIOLOGY LECTURER: BRIAN ALLISON MARTOS DATE OF LECTURE: FEBRUARY 8, 15, & 29, 2024 II. III. I. Introduction What is Physiology? Physiological Processes are Products of Evolution Physical processes = adaptations We are products of mil...

20373-X: ZOOLOGY 120 ANIMAL PHYSIOLOGY | LECTURE FOUNDATIONS OF PHYSIOLOGY LECTURER: BRIAN ALLISON MARTOS DATE OF LECTURE: FEBRUARY 8, 15, & 29, 2024 II. III. I. Introduction What is Physiology? Physiological Processes are Products of Evolution Physical processes = adaptations We are products of millions of years of evolution Mechanisms that lead to evolution: ○ Natural selection: survival of the fit enough; organisms that are more adapted to their environment are more likely to survive and pass on the genes that aided their success. This process causes species to change and diverge over time. ○ Randomized variation: also affects natural selection Physiology: biological sub-discipline that deals with functions in living organisms ○ The study of the functions of organisms, or how life works Metabolism, homeostasis, reproduction ○ The science that seeks to explain the physical and chemical mechanisms that are responsible for the origin, development, and progression of life Goal of Physiology: LEVELS OF EXPLANATION ○ To explain the fundamental mechanisms that 1. Mechanistic explanation operate in a living organism and how they interact ○ How does it work? ○ Understand, at the molecular level, the mechanisms ○ Ex: bifurcated tail of Schistosoma behind the physiological functions that present in a 2. Evolutionary explanation living ○ How did it evolve to be this way? Two types of ○ Ex: Conus ○ Animal Physiology i. Divergent evolution ○ Human Physiology ii. Natural selection Automation: machine that is made to imitate a iii. Homologous traits human→ by studying human themselves(due to iv. Analogous traits interest) 3. Teleological approach Clinical Correlation ○ What is the purpose? ○ Invasive diagnostic techniques: done by cutting or ○ Phenomena that occur in organisms are explained in entering a body part using medical instruments terms of their particular purpose Auscltation, Percussion, Palpation (a bit ○ Ex: function of hypothalamus invasive) ○ Non-invasive diagnostic techniques: non-invasive Adaptations reflect evolutionary history including tests do not require breaking the skin or entering cost-benefit trade-offs the body ○ Evolution builds on the past and therefore is often constrained by it, and selection often involves trade-offs and compromises Multiple ova of Taenia saginata to increase chances of infection Chicks of chicken are limited because enough energy and care is given to all JA N A H Figure 1. Vitruvian Man by Leonardo da Vinci A N G EL IK A 2023-2024 A N TO N IO OUTLINE Introduction IV. Membrane Physiology A. What is A. Overview of Physiology? Membrane Levels of Organization Transport A. Cell B. Unassisted B. Tissue Membrane C. Organ Transport D. Organ System C. Assisted E. Organism Membrane Homeostasis Transport A. History D. Membrane B. Review Structure and C. Homeostasis and Function Regulation E. Cell-to-Cell D. Homeostatic Adhesions Control SYstems F. Membrane E. Feedback Loop Potential F. Tonic Control I. 2ND SEMESTER Physiology As A Discipline Integrative Discipline ○ Anatomy ○ Physics ○ Chemistry ○ Biochemistry ○ Molecular Biology TRANSCRIBED BY: JANAH ANGELIKA R. ANTONIO | BIOLOGY 1 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY ○ Ecology Comparative Discipline ○ Often following the Krogh principle ○ “For such as large number of problems, there will be some animal of choice, or a few such animals, on which it can be most conveniently studied” II. Levels of Organization Cell The level of organization that carries the genetic information to tell what organism it came from. Three main parts: ○ Nucleus: storage of genetic material ○ Plasma membrane: protection and controls what goes in and out of the cell(maintains balance) ○ Cytoplasm: where organelles are found Conditions inside the cell should be optimal for the cell to function Figure X. Animal cell. Tissue Figure X. Title. Connective Tissue A group of cells with similar structures and functioning together as a unit. A nonliving material, called the intercellular matrix, fills the spaces between the cells. This may be abundant in some tissues and minimal in others. Four types: ○ Connective tissue ○ Epithelial tissue ○ Muscle tissue ○ Nervous tissue JA N A H A N G EL IK A They perform various functions, including protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception. Functions as a lining for most organs Cells found here are categorized based on shape. ○ Squamous ○ Cuboidal ○ Comlumnar Depending on the number of layers, the tissue is divided into simple or stratified. Subclassifications include pseudostratified, ciliated, or transitional. Glandular epithelial cells produce and release various macromolecules. transitional epithelium(urothelium)— made up of several layers of cells that become flattened when stretched pseudostratified epithelium— made up of closely packed cells that appear to be arranged in layers because they're different sizes, but there's just one layer of cells. A N TO N IO They attach organs and tissues together. They store fat in the form of adipose tissues. They help in repairing tissues. Function as support to organs and cells, transport nutrients and wastes, defend against pathogens, store fat, and repair damaged tissues. Connective tissue is composed primarily of an extracellular matrix and a limited number of cells. Adipose or fat tissues 2 Main Components ○ Extracellular matrix ○ Cells Figure X. Four types of epithelial tissue. Figure X. Title. Epithelial Tissue Forms the covering of all body surfaces, line body cavities, and hollow organs, and is the major tissue in glands. Embryonic Connective Tissue (Specialized) Mesenchymal connective tissue— the connective CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 2 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY tissue of an embryo, consists of mesenchymal cells in a gel-like amorphous ground substance containing scattered reticular fibers. ○ Mesecnhyme— from mesoderm; gives rise to most tissues, such as skin, blood, or bone Bone tissue: ○ Lacunae: Black/dark areas that contain osteocytes Osteocytes: regulate local mineral deposition and chemistry at the bone matrix level ○ Canaliculi: connects one lacuna to the other; communication for osteocytes Cartilage: ○ Hyaline cartilage: has lacunae, and inside of it are chondrocytes) Found in joints ○ Fibrocartilage: has collagenous fiber in its matrix Found in vertebral column ○ Elastic cartilage: supports parts of your body that need to bend and move to function Found in nose and ears; epiglottis A N G EL IK A A N TO N IO Figure X. Title. Other Specialized Embryonic Tissue Loose connective tissue: most widely distributed connective tissue ○ holds organs, anatomic structures, and tissues in place. The extracellular matrix is the most significant feature of loose connective tissue with large spaces between fibers. Adipose tissue: provides energy storage, insulation from extreme temperatures, and cushioning around soft organs White fibrous tissue of tendon: ○ White fibrous tissues arise in two forms: tendons and sheath. ○ Tendons: joins skeletal muscles to bones; They are the thick bundle of collagen fibers that run parallel to each other. Due to the presence of collagen fibers, they are strong, and flexible but inextensible. JA N A H 💡 Red blood cell: ○ Remember Connective cells contain cells and ECM→ liquid portion of the blood will be the ECM Figure X. Title. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 3 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Muscular Tissue It controls the movement of an organism Three main types; ○ Cardiac(involuntary) ○ Skeletal(voluntary) ○ Smooth(involuntary) Figure X. Components of the ECF Figure X. Title. A N TO N IO Nervous Tissue Flow of exchange between the body’s external and internal environment; exchange of O2(from internal→ECF→cells) and CO2(from cells → ECF →outside cell) ○ Intracellular fluid: ○ Extracellular fluid: privately maintained Plasma and interstitial fluid ○ Plasma membrane separate the ICF and ECF and maintain the environment of ECF Found in the brain, spinal cord, and nerves. It is responsible for coordinating and controlling many body activities. It stimulates muscle contraction, creates an awareness of the environment, and plays a major role in emotions, memory, and reasoning. Neurons: cells in the nervous tissue Figure X. Components of the ECF Homeostasis and Regulation Figure X. Title. Organ systems Whole-body systems ○ Integumentary and Nervous System Support and movement systems ○ Skeletal and Muscular System Maintenance systems ○ Endocrine, Cardiovascular, Lymphatic, Respiratory, Digestive, Urinary, and Reproductive Systems III. Homeostasis JA N A H History Claude Bernard (1859) Homeostasis and regulation are different but related Homeostasis: maintaining a particular state in the phase of disturbances ○ Will try to maintain the natural state when there is a disturbance Regulation: produce the optimum condition Homeostasis refers to the preservation of a constant internal environment within an organism, whereas regulation refers to the management of a specific process or system. Homeostasis is maintained by mass balance and mass flow ○ Mass balance: In an open system, to maintain a constant level, the output must be equal to the input; open system ○ Mass flow: Mass balance = existing body load or metabolic production + intake - excretion or metabolic removal A N G EL IK A “la fixité du milieu intérieur et la condition de la vie libre” “One condition of a free and independent life is a constant internal environment” Walter B. Cannon (1939) Coined the term homeostasis Review Body cells are in contact with a privately maintained internal environment, instead of with the external environment that surrounds organisms Figure X. (a) Mass balance in an Open system and (b) mass balance in the body. Cells make up our systems. They like to maintain a constant internal environment. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 4 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Figure X. Interdependent relationship of cells, body systems, and homeostasis. Homeostatic control systems: functionally integrated/interconnected networks of body organs; for regulating a disturbance Figure X. Example of the homeostatic control system. Figure X. Title. Within desired range: no action required Outside the desired range: sensor is activated, integrating center will analyze, then alter the effector to influence the regulated variable to fall on desired range. Homeostasis is not a fixed state, but instead a dynamic Figure X. (a) Capuchin monkey (b) Monarch butterfly (c) Marine shells steady state. Levels of Homeostatic Control Systems: Components of Homeostasis 1. Intracellular Level— within a cell ○ Stimulus— disturbance that will be received by an 2. Local or Intrinsic Level— within an organ organism 3. Reflex Control or Extrinsic Level— utilized by organ ○ Receptor or Sensor— receives the stimulus; systems; with the help of hormones; endocrine ○ Integrator— processes information from the system sensors and sends signals or commands to effectors. Compare the received signal of stimulus to a Feedback Loop set point or the ideal state Status of body conditions is monitored, evaluated, Give the correct response changed, remonitored, and reevaluated. ○ Effector— takes actions to restore the environment Negative Feedback to a steady state. Pathways in Homeostasis Negative feedback is the main regulatory mechanism for ○ Afferent— a pathway that will be taken from the homeostasis sensor going toward the integrator Oppose the stimulus ○ Efferent— where information flows from the Negative feedback (or balancing feedback) occurs when control center to the effector some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. JA N A H Animals vary in their homeostatic abilities ○ Regulators: use internal mechanisms to defend a relatively constant state; Figure Xa ○ Conformers: internal state varies with that of the environment; Figure Xc ○ Avoiders: may not be capable of internal regulation but can minimize internal variations by avoiding environmental disturbances; Figure Xb A N G EL IK A A N TO N IO Homeostatic Control Systems Figure X. Summary of a mechanism of homeostatic control system. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 5 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY more production of pepsinogen Secretion of food from the stomach will stop the secretion of HCl→ pepsinogen breakdown will stop→ [pepsinogen] will increase A N TO N IO ○ Figure X. Title. Figure X. Negative feedback. (a) components of negative feedback control system. (b) Negative-feedback control of room temperature. (c) Negative feedback control of mammalian body temperature Example: Uterine contraction ○ Contraction of the uterus during childbirth causes the release of oxytocin, which stimulates stronger contractions of the uterus, causing more oxytocin release. This perpetual cycle results in a positive feedback response. ○ Delivery of baby stops the cycle A N G EL IK A INADEQUACIES OF NEGATIVE FEEDBACK 1. Delayed response ○ Remember that the stimulus has a lot of pathway to pass through before reaching the effector. 2. Delay in shutting effector 3. Unable to adapt to a new environment Positive Feedback Amplifies the stimulus for a body’s response In a continuous cycle so it needs an external factor to shut off the feedback Strengthen or reinforce a change in one of the body’s controlled conditions Control self-perpetuating events that can be out of control and do not require continuous adjustment. In positive feedback mechanisms, the original stimulus is promoted rather than negated. Positive feedback increases the deviation from an ideal normal value. Example: Pepsinogen and HCl in digestion ○ The activation of the digestive system enzyme pepsin is an example of a positive feedback mechanism. Eating food triggers the stomach to release a protein called pepsinogen. Hydrochloric acid in the stomach then converts the pepsinogen into the active enzyme pepsin. This will result in Figure X. Title. Tonic Control JA N A H SOLUTIONS IN NEGATIVE FEEDBACK 1. Anticipation or Feedforward System: homeostatic control system in which the anticipatory effect that one intermediate exerts on another intermediate further along in the pathway allows the system to anticipate changes in a regulated variable. ○ Fast action 2. Acclimatization Systems: a process of biological adaptation when exposed to environmental factors such as hypoxia, cold, and heat for prolonged periods, where non-genetical variations play a role in allowing subjects to tolerate hypoxic, cold, or hot environments. ○ Alteration of existing feedback system ○ Days or months Tonic control regulates physiological parameters in an up-down fashion. ○ signal is always present but changes in intensity Example: neuron and blood vessel ○ Neuron sends moderate signals towards a blood vessel that results in intermediate diameter ○ Decrease in signal rate results in dilation of blood vessel ○ Increased signal rate results in constriction of blood vessel Figure X. Tonic Control. Antagonistic Control CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 6 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Two responses contradicting each other Example: blood glucose ○ High blood glucose Trigger β cells of the pancreas to release insulin that will lower the level of the blood glucose Insulin reduces the body's blood sugar levels and provides cells with glucose for energy by helping cells absorb glucose. Inhibit the α cells from producing glucagon to lower the level of the blood glucose Glucagon triggers the liver to convert stored glucose (glycogen) into a usable form(glucose) and then release it into your bloodstream through signal transduction. ○ Low blood glucose Trigger α cells to release glucagon that will help raise the blood glucose to normal Inhibit the β cells from producing insulin to raise the level of the blood glucose to normal Example: Callinectes sapidus or blue crabs that can live in high salinity and low salinity due to their oxygen binding effectiveness of hemocyanin Pathophysiology For homeostasis to occur(replenishment of cells), cell death/apoptosis should be replaced by cell division A N G EL IK A Pathophysiology— Disturbances in physiological processes the eventually leads to diseases For wellness to be achieved, input=output output>input→leads to illness A N TO N IO Figure X. Antagonistic control in controlling blood glucose level via insulin and glucagon. Example: neurons in controlling heart rate ○ Sympathethic neuron: results to increaased heart rate ○ Parasympathetic neuron: results to decreased heart rate IV. Membrane Physiology Transport JA N A H Figure X. Antagonistic control caused by sympathetic and parasympathetic neurons in heart rate. Enantiostasis Figure X. Title. Enantiostasis— Maintenance of metabolic and physiological functions in response to variations in the environment; consistency of function achieved by changing one physiological variable to counteract a change in another ○ The survival of species that live in an environment such as an estuary, where salt and water concentrations fluctuate broadly on a daily basis, depends on their ability to either avid these changes of tolerate them Na-K pump: ○ Open to ECF, the carrier protein drops off sodium on its high-concentration site and takes up K from its low-concentration site ○ ↑ [K] in the cell; ↑ [Na] outside the cell ○ Dephosphorylated will have high affinity for K ○ Will there be channels that allow the diffusion? Yes. If no channels, there will come a time when ICF will lose Na channels and ECF will lose K channels Secondary Active Transport— takes advantage of the concentration gradient that is created by a primary active transport ○ A cotransport carrier at the lumina of the intestine bonds simultaneously transfers glucose against a concentration gradient and Na down on concentration gradient from the lumina to the cell Initially, there will be a high concentration of glucose(from the food) inside the cell. And when you eat, you will have glucose outside the cell The glucose in the lumen has to go inside the cell for it to be transported into the different parts of the body. Glucose needs to enter the intestinal cell(already has a high concentration of glucose) ○ No energy is directly used by the cotransport carrier to move glucose uphill CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 7 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY The operation of the cotransport is driven by the Sodium concentration gradient Glucose will be transported inside the cell along with Na. [Na] is higher outside the cell → movement is high to low Low [Na] inside because of the Na-K pump Glucose takes advantage for it to be able towards the inside of the cell Na-K pump actively transport Na out of the cell which lowers the concentration inside the intestinal cell After entering the cell by secondary active transport, glucose is transported down to its concentration gradient from the cell Continuous blood flow in the blood vessel→ glucose will move along Types of Transport Figure X. Tonicity of a cell. Factors that affect the rate of net diffusion of a substance across a membrane Magnitude of concentration gradient ↑ concentration gradient = ↑ rate of net diffusion ↑ Surface area = ↑ rate of net diffusion Lipid solubility ↑ solubility = faster rate of diffusion Molecular weight ↑ molecular weight = ↓ rate of net diffusion Distance ↑ distance = ↓ rate of net diffusion A N TO N IO ○ A N G EL IK A ○ Cells are selectively permeable that will allow the passage of certain materials Antiport vs Symport: ○ Antiport: when two kinds of molecules move in the opposite directions while diffusing through carrier proteins. Example: Na+-K+ pump ○ Symport: when two kinds of molecules move in the same direction while diffusing through carrier proteins. Example: Na+ co-transport carrier Membrane Transport JA N A H TYPES OF MEMBRANE TRANSPORT 1. Unassisted Membrane Transport— does not necessarily need a protein to happen ○ Diffusion— if a substance can permit the membrane, the molecules will move from high concentration to an area of low concentration; passive process; Occurs because of the particles’ kinetic energy Tonicity Hypotonic— solute concentration outside the cell is lower compared to inside the cell→ swelling of cell Hypertonic— concentration of solutes is higher compared to inside the cell; shrinking of cell Isotonic— any external solution that has the same solute concentration and water concentration; no net movement of water will take place. Osmosis— movement water; water tends to move towards an area with higher solute concentration Assisted Membrane Transport— carrier-mediated; the key molecule is protein ○ Carrier-mediated transport— ○ Facilitated diffusion transport— Substances move from a higher concentration to a lower concentration; Proteins that have an affinity to a particular molecule Requires carrier molecule Means by which glucose is transported into cells When the carrier protein is facing the outside of the cell, the molecule will bind to binding sites inside the carrier protein Once the molecules are bound to the binding sites, the is a conformational change in the ○ 2. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 8 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY carrier protein. When it opens towards the ICF, the affinity for the molecule lowers thus releasing the molecule towards the ICF Then it will return to its initial conformation ○ Active transport— Moves a substance against its concentration gradient Requires a carrier molecule that will use the energy Primary active transport Requires direct use of ATP Secondary active transport Driven by an ion concentration gradient established by a primary active transport system Types of Active Transport: Primary— direct use of ATP; carrier protein will be phosphorylated Active: [TIMESTAMP 20:00] ○ Upon dephosporylation, there is a conformational change that ○ [NA/K pump] Secondary— driven by an ion concentration gradient established by a primary active transport system In assisted membrane transport: In assisted membrane transport: ○ Types of Transport (carrier mediated) Membrane transport— Passive— without the use of energy; carrier mediated Active— requires energy Vesicular transport— transport materials in bulk; use of vesicles A N TO N IO Figure X. Title. Are all endocytotic processes receptor mediated? No. Phagocytosis and pinocytosis Exocytosis— materials are secreted and moved outside the cell ○ Constitutive exocytosis— requires no signal is required for releasing the secretory materials outside the cell and is called constitutive exocytosis ○ Regulative exocytosis— requires an external signal for releasing secretory materials outside the cell is called regulated exocytosis A N G EL IK A Vesicular Transport 2. transport materials in bulk; use of vesicles Active method of transport Structure and Function of the Plasma Membrane JA N A H TWO TYPES OF VESICULAR TRANSPORT 1. Endocytosis— materials are moved into the cell ○ Phagocytosis— transfer of large solid particles ○ Pinocytosis— intake of liquids into the cell along with small solutes ○ Receptor–Mediated Endocytosis— require a receptor to be taken by the cell In many cases, the plasma mebrane has to internalize and reconstitue the proteins that will be comprising the plasma membrane Clathrin mediated endocytosis Cargo proteins— recognition by cargo receptor Adaptin—for recognition to happen, cargo receptor should bound to a cytosolic domain of protein known as adaptin This signal adaptor recognition will form a pit where the cargo receptors are concentrated Clathrin— covers the area where the pit is forming Dynamin— GTpase enzyme which depends on the hydrolysis of GTP/GDP; act as molecular scissor where it causes the pit will eventually bud off into the cytoplasm forming a vesicle (clathrin coated vesicle) The vesicle will unnderog the process of uncoating such that the adaptin and clathrin sturcutres will be reused The uncoated vesicle is now ready to use by the cell Physical barrier: establishes a flexible boundary, protects cellular components and supports cell structure. Phospholipid bilayer separates substances inside and outside the cell Selective permeability: regulates the entry and exit of ions, nutrients, and waste molecules through the membrane; total control of the materials going in and out of the cell Electrochemical gradients: establishes and maintains the electrical charge difference across the plasma membrane; ions have charges Communication: contains receptors that recognize and respond to molecular signals Intercellular connection: connections with other cells Communication and the intercellular connection is dependent on the glycocalyx ○ Glycocalyx— collective term for the carbohydrates molecules that are attached to the plasma membrane Remember that the plasma membrane will be having proteins and heads of the phospholipids which are connected to a carbohydrate-protein Oligosaccharide chains that constitute the glycocalyx All carbohydrates that are found outside the the cell Functions as “molecular fingerprint” CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 9 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Figure X. Title. Figure X. Title. Fluid Mosaic Model A N G EL IK A Phospholipid— major lipid components of the membrane ○ Phospholipid is amphipathic in nature hydrophilic: due to polar head group by phosphate) hydrophobic: due to nonpolar tail group–saturated and unsaturated) Saturated: straight; 3 H molecules Unsaturated: kink due to double bond between carbons; 2 H molecules only Cholesterol— also amphipathic due to the presence of hydroxyl group ○ situates itself in between the phospholipids to help stabilize the membrane. ○ Cholesterol also plays an important role in regulating membrane fluidity during changes in temperature ○ Plasma membrane is comprised of 30-40% cholesterol ○ At high temperatures, cholesterol acts to stabilize the cell membrane and increase its melting point; while at low temperatures, it inserts into phospholipids and prevents them from interfering with each other to avoid aggregation or compact ○ Prevent the phospholipids from separating away from each other When we try to look at the plasma membrane under a powerful microscope, we can see different patterns of molecules that look like a mosaic ○ Peripheral proteins— ○ Transmembrane proteins— proteins that completely span the cell membrane Fluid because the molecules are constantly moving in a fluid manner When frozen during cryofracture, usually they are separated ○ P(protoplasmic) face– most of the proteins will be embedded here Each protein has corresponding depth in the other face ○ E(extracellular) face– lesser proteins A N TO N IO JA N A H Figure X. Title. Lipid rafts– portions of the plasma membrane that are less fluid due to higher concentration of cholesterol Integral Proteins Figure X. Title. Embedded in the plasma membrane of the cells Channels— proteins that allow entry and exit of molecules Pumps— Na-K pumps; energy-dependent carrier proteins Carriers— passive diffusion Docking marker acceptors— receptors that are essential for exocytosis for recognition of vesicles Membrane-bound enzymes— Receptor sites— Cell adhesion molecules (CAMs) ○ Integrins— molecules that attach to the ECM, usually essential for cell migration ○ Cadherins— Calcium-dependent dependent molecules Cell surface markers— CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 10 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Collagens Elastins Figure X. (a) Title, (b) , and (c) ____. Adhesion Proteins Fibronectins— adhesion of the cell towards ECM → integrins and fibronectins Laminins— integrins may also bind to the basal lamina Membrane Nanotubes/Cytonemes Cell-Cell Adhesion Proteins Cadherins Selectins (blood cells) — white blood cells Integrins Cell to Cell Adhesions Membrane Potential JA N A H Extracellular Matrix ○ Serves as biological “glue” ○ Major types of protein fibers interwoven in matrix ○ collagen, fibronectin, elastin Collagen and fibronectin— where integrins(intracellular) will be binding to Elastin— proteins that are prone to stretching Can be seen in lungs, skin, and blood vessels(artery) CAMs in cells’ plasma membrane— ○ Cadherin— found attached to the actin of the cytoskeleton via cathenins Specialized Cell Junctions ○ Desmosomes— act like “spot rivets” that anchor two closely adjacent nontouching cells Intracellular and extracellular filaments ○ Gap junctions (communicating junctions)— Small connecting tunnels formed by connexons; In nonmuscle tissues permit unrestricted passage of small nutrient molecules between cell ○ Tight junctions (impermeable junctions)— Firmly bond adjacent cells together; Seal off the passageway between the two cells Glycocalyx/cell coat is the molecular fingerprint of each cell types that allows other cells to recognize them Glycolipid— carbohydrate moity is attached to phspholipid Glycoprotein— carbohydrate bound to proteins Nerve and muscle cells— excitable cells have resting membrane potential Do all cells have membrane potential? Yes but not all cells are excitatory Remember that Na+—K+ pump transport Na+ ions outside the cell and K+ ions is transported inside the cell(against concentration gradient) Leak channels— entry and exit of ions based on their concentration gradient A N G EL IK A Intercellular communication between distant cells found in specific types of cells. May allow the transport of specific molecules between two cells Carbohydrates Cell-Matrix Adhesion Protein A N TO N IO Structural Proteins Figure X. Title. Potassium and Anionic proteins ○ Anions found inside the cell cannot pass through the membrane due to its very large size ○ K+ ions pass through the plasma membrane from ICF to ECF (concentration gradient) Overtime, the inside of the cell becomes more ○ negatively charged due to anionic proteins, thus creating an electrical gradient. ○ K+ ions will then return to the ICF to balance the charge ○ When the electrochemical gradient counterbalances the concentration graident, it is known as the equilibrium potential (EK+ is -90 mV.) ○ Resting membrane potential is –70 mV CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 11 LECTURE 1 - FOUNDATIONS OF PHYSIOLOGY | ANIMAL PHYSIOLOGY Subsubtopic 1 content Subsubtopic 1 Figure X. Title. Sodium and Chloride ions ○ Leak channels will allow the entry of Na+ ions ○ The inside of the cell becomes positively charged. ○ The ECF will attract Na+ ions because of electrical gradients Figure description ○ There are more leak channels for K+ A N G EL IK A content A N TO N IO Figure X. Title. V. Quizzes JA N A H Quiz 1 Nerve and muscle cells – excitable cells -have resting membrane potential Quiz 2 1-3) Inadequacies of negative feedback mechanisms 4.) Compare and contrast the regulatory mechanisms of regulators, confomers, and avoiders. 5.) T/F. Facilitated diffusion uses energy. 6-8.) Factors that directly affect the rate of net diffusion 9.) Define secondary transport CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 12 20373-X: ZOOLOGY 120 ANIMAL PHYSIOLOGY | LECTURE NEURONAL PHYSIOLOGY 2ND SEMESTER 2023-2024 LECTURER: BRIAN ALLISON MARTOS DATE OF LECTURE: MARCH 7 & 12, 2024 II. III. I. Introduction Overview Figure X. Decremental spread of graded potentials. Figure X. Title. Current flow of graded potential ○ Example: a membrane experienced a triggering event of a stimulus → opening of voltage-gated Na+ channels → influx of Na+ ions → neutralize the negative charge of the cell → results to depolarization Na+ concentration is higher on the outside ○ Active area— the nearest area where Na+ ions enter; there is a local, passive flow of current from the active site to the inactive site(adjacent to it) Local current flow will allow the flow of charges towards both directions of the inactive site. ○ The direction of flow of current is established by the flow of positive ions A N G EL IK A Excitable cells such as neurons and muscles evolved for rapid signaling, coordination, and movement ○ Allow changes in membrane electrical state Every cell has a certain membrane potential that is important for rapid signaling, coordination and movement Communication is an important part of homeostasis ○ Communication is critical for the survival of the cells that compose the body. Polarization— the value of the membrane potential is not 0 mV ○ May either be positive or negative longer the duration of the graded potential Local changes in membrane potential that occur in varying grades or degrees of magnitude or strength When the area of the cell membrane is triggered by a stimulus, a graded potential may happen; decrease decrementally Initial active area → graded potential travels(example: 14 mV) → *example: 7 mV on both sides A N TO N IO OUTLINE Introduction IV. Synapses and Integration A. Overview A. Subtopic 1 Graded Potentials V. Neural Signaling and A. Graded Potential External Agents Action Potential A. Subtopic 1 A. Introduction B. Axon Hillock C. Action Potential Propagation D. Axon terminal I. JA N A H DIFFERENT MEMBRANE ELECTRICAL STATES 1. Depolarization ○ remove the charge or polarized nature of the cell; approaches 0 ○ change in potential that makes the membrane less polarized than at resting potential When there is an inward flow of positive ions, the inner lining of the PM becomes more positive 2. Repolarization ○ bringing the charge towards the resting membrane potential after depolarizing 3. Hyperpolarization ○ increase the polarization → approaching the negative ○ a change in potential that makes the membrane more polarized than at resting potential The membrane is less positive and more negative Figure X. Types of changes in membrane potential. II. Graded Potentials Graded Potential Short distanced signals that decay over time The stronger a triggering event, the larger the resultant graded potential The longer the duration of the triggering event, the Figure X. Current flow during a graded potential. (a) The membrane of an excitable cell at resting potential. (b) A triggering event opens ion channels, usually leading to net Na+ entry that depolarizes the membrane at this site. The adjacent inactive areas are still at resting potential. (c) Local current flows between the active and adjacent inactive areas, resulting in depolarization of the previously inactive areas. In this way, the depolarization spreads away from its point of origin. TRANSCRIBED BY: JANAH ANGELIKA R. ANTONIO | BIOLOGY 1 LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY Voltage–gated Na+ channel is back at its original conformation → closed but capable of opening On return to resting potential, Na+ activation gate closes and inactivation gate opens, resetting channel to respond to another depolarizing triggering event Further outward movement of K+ through still-open K+ channel briefly hyperpolarizes membrane, which generates after hyperpolarization Hyperpolarization happens also because K+ channels close slowly K+ activation gate fully closes, and membrane returns to resting potential ○ ○ Figure X. Current loss across the plasma membrane leading to decremental spread of a graded potential. III. Action Potentials Introduction Brief, rapid, and large (100 mV) changes in membrane potential during which potential actually reverses so that the inside of the excitable cell transiently becomes more positive than the outside A N TO N IO ○ What brings back the concentrations of ions in and out of the cell? Na+–K+ pump Figure X. Title. A N G EL IK A Figure X. Changes in membrane potential during an action potential. Spike/firing Phenomenon of rapid potential reversal propagated in nondecremental fashion; not diminished as it travels across the plasma membrane Involves only a small portion of the total excitable cell membrane Do not decrease in strength as they travel from their site of initiation throughout remainder of cell membrane Phases of action potential ○ From –70 mV, there will be a stimulus that will open the voltage-gated Na+ channels ○ Stimulus could create graded potentials → depolarization proceeds slowly K+ channels are still closed ○ Threshold potential –50 to –55 mV Triggers action potential Explosive depolarization: Many voltage–gated N+ ion channels open and many N+ ions pass through Sharp upward deflection as the potential rapidly reverses itself so that the inside of the cell becomes positive compared to the outside Once action potential is achieved, the inactivation gate of Na+ is slowly closed Slow opening of voltage–gated K+ channels ○ At the peak: The slow closing of inactivation gate is already done → no more entry of Na+ ions Opening of voltage–gated K+ channels → exit of K+ ions → the cell is becoming negative Repolarization— dropping back to resting potential JA N A H VOLTAGE–GATED CHANNELS INVOLVED IN THE FORMATION OF ACTION POTENTIAL 1. Voltage–gated Na+ channels ○ Activation gate— hinged door that opens or closes depending on the voltage or change in resting membrane potential ○ Inactivation gate— ball and chain sequence of amino acids that are facing the ICF ○ States of voltage –gated Na+ channels: i. Closed but capable of opening— activation gate may open depending on the change in resting membrane potential ii. Open(activated)— allow the influx or entry of Na+ ions inside the cell iii. Closed and not capable of opening(inactivated)— inactivation gate(ball and chain) binds to a receptor in the channel that closes it Figure Xa. Conformations of voltage-gated sodium channels. 2. Voltage–gated K+ channels Figure X. Conformations of voltage-gated sodium and potassium channels. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 2 LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY For an action potential to happen in a cell, it should first reach a threshold potential(through graded potential) Activation gate of Na+ will open ○ K+ channels are still closed Permeability of Na+ and K+ during action potential ○ Almost similar trend of permeability of Na+ with an action potential. Why? ○ Permeability of K+ will increase at the peak of action potential 1. 2. Resting potential: all voltage-gated channels closed. At the threshold, Na+ activation gate opens and PNa+ rises. Na+ enters the cell, causing explosive depolarization to +30 mV, which generates a rising phase of the the action potential. At the peak of the action potential, the Na+ inactivation gate closes and PNa+ falls, ending the net movement of Na+ into the cell. At the same time, the K+ activation gate opens and PK+ rises. K+ leaves the cell, causing its repolarization to resting potential, which generates a falling phase of action potential. On return to resting potential, the Na+ activation gate closes and inactivation gate opens, resetting the channel to respond to another depolarizing triggering event. Further outward movement of K+ through a still-open K+ channel briefly hyperpolarizes the membrane, which generates after hyperpolarization. K+ activation gate closes, and the membrane returns to resting potential. 3. 4. 5. 6. 7. JA N A H 8. Cell body/soma— nucleus and organelles are found; input zone Dendrites— receive signals of information from other neurons; input zone Axon— send signals from the soma ○ Conducting zone or passageway of information from the cell body ○ Give off branches known as collaterals that will end up in in the axon terminal ○ Axon terminal may innervate other neurons(either dendrites, soma, or muscle cells) Action potentials are propagated from the axon hillock to the axon terminals ○ Neuron’s trigger zone; the site where action potentials are triggered by a graded potential if it is of sufficient magnitude; where depolarization first happens A N G EL IK A Axon Hillock A N TO N IO Figure X. Permeability changes and ion fluxes during an action potential. Figure X. Anatomy of a typical neuron. Action Potential Propagation Contiguous conduction Table 1. Comparison of Graded Potentials and Action Potentials. the spread of action potential occurs along every patch of the membrane down the length of the axon Pathway: ○ Action potential is produced at action hillock Initial active area where AP is produced ○ Influx of Na+ ions in the active area Local, passive flow of Na+ ions to neutralize the charges in the adjacent inactive area → this will trigger the portion of the axon to be positive then depolarize ○ Initially inactive, the area will eventually reach threshold then will undergo action potential CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 3 LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY the membrane 2 important myelin-forming cells: #mnemonics–”COPS”# Schwann cells in PNS Oligodendrocytes in CNS Description Figure X. Contiguous conduction. What ensures the one-way propagation of action potential? ○ Refractory periods— mainly caused by the changing states of both the voltage-gated Na+ and K+ channels ○ 2 types Absolute Refractory Period— a point where another action potential cannot be initiated Voltage-gated Na+ channels will never open unless action potential is done Cannot be triggered by any stimulus Relative Refractory Period— after the ARF; the portion of the membrane can be stimulated to produce an action potential; however it needs stronger stimulus because there is hyperpolarization Figure X. Saltatory conduction. Axon Terminal Synapse— junctions between two neurons or neuron to muscles ○ Presynaptic neuron— Axon terminal is known as synaptic knob Synaptic know will contain synaptic vesicles Inside the synaptic vesicles are the neurotransmitters ○ Postsynaptic neuron— have receptors for the receiving of neurotransmitters Receptors are located in the subsynaptic membrane JA N A H A N G EL IK A A N TO N IO ○ Process ○ Presynaptic When the action potential reaches the synaptic knob, it will open voltage-gated Ca2+ channels Ca2+ ions have a high concentration in the ECF, thus the opening of the channels allow the entry of ions When Ca2+ ions enter the synaptic knob, it will trigger the release of neurotransmitters via exocytosis Release of neurotransmitters in the synaptic cleft ○ Postsynaptic Neurotransmitter will bind to the receptors that are chemically-gated → opening of receptors(may be specific or non-specific) When the action potential waveform reaches the presynaptic axon terminal, it alters the activity of the target cells on which the neuron terminates. There are only two basic kinds of transmission of signals at this point: electrical (direct) or chemical (indirect), which differ in signal transfer mechanisms. Although electrical transmission is not as common as chemical, it is much simpler. Figure X. Absolute and relative refractory periods. Saltatory conduction the impulse “jumps” from node to node (nodes of Ranvier), skipping over the myelinated sections of the axon ○ Propagates action potentials more rapidly because the action potential leaps over myelinated sections ○ In the nodes of Ranvier, there should be rich number of voltage-gated Na+ channels Myelination increases the speed of conduction of action potentials and conserves energy in the process ○ Myelin sheath acts as an insulator to prevent current leakage across the myelinated portion of CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 4 LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY IV. Synapses and Integration Synapses Presynaptic Neuron ○ Traveling of action potential from axon towards synaptic knob → Action potential opens up voltage-gated Ca2+ channels → influx of Ca2+ into the synaptic knob ○ Synaptic knob that contain synaptic vesicles that has neurotransmitters is triggered ○ Neurotransmitters released via exocytosis in the synaptic cleft Postsynaptic Neuron ○ Have receptors for particular neurotransmitter ○ Once neurotransmitters bind to receptors, there will be open of chemically-gated receptor channels ○ Chemically-gated receptor channels will be dependent on the type of postsynaptic neuron Non-specific ion channels (Na+ and K+) or Cl– A N TO N IO the opening of non specific cation channels in the subsynaptic membrane that permit simultaneous passage of Na+ and K+ through them How does it depolarize a postsynaptic neuron? Opening of chemically-gated channels (Non-specific channel for Na+ and K+) ○ Na+ concentration is ↑ in the ECF AND ↓ in the ICF. Meanwhile, K+ concentration is ↑ in the IFC and ↓ in the ECF ○ Movement of Na+ ions is towards inside when non-specific channel opens that make the ICF become more positive ○ However K+ ions may still exit the cell which makes the ICF more negative in terms of K+ ion movement only ○ Considering the electrical gradient: The charge of the ICF is negative By considering electrical gradient, the negatively charged proteins inside the cell will attract positively charged Na+ Two gradients triggers Na+ ions to go inside: concentration and electrical gradient Concentration gradient of K+ triggers K+ ions to go outside. However the inside of the cell is negatively charged. So the electrical gradient of the cell attracts K+ ions Contrasting event for K+ ions Entry of Na+ is higher is higher than the exit of K+ Net movement of K+ is still towards the outside, however its rate is much slower compared to the entry of Na+ ions. EPSPs are very small graded potential ○ It’s still excitatory because it will cause depolarization JA N A H A N G EL IK A EVENTS IN SYNAPSE 1. When an action potential in a presynaptic neuron has been propagated to the axon terminal, this change in potential triggers the opening of voltage-gated Ca2+ channels in the synaptic knob. 2. Because Ca2+ is in a much higher concentration in the ECF, and because the cell has a negative charge, this ion flows into the synaptic knob through the opened channels (step 2). 3. Ca2+ induces the release of a neurotransmitter from some of the synaptic vesicles into the synaptic cleft (step 3). The release is accomplished by exocytosis 4. The released neurotransmitter diffuses across the cleft and combines with specific protein receptor sites on the subsynaptic membrane, the portion of the postsynaptic membrane immediately underlying the synaptic knob Inhibitory Synapses (sub means “under”) (step 4). Hyperpolarization (greater internal negativity) 5. This binding triggers the opening of specific ion channels ○ Opening of Cl– ions in the subsynaptic membrane, changing the permeability ↑ concentration outside, ↓ concentration inside of the postsynaptic neuron (step 5). These are chemically ○ Charge inside the cell becomes more negative when gated channels, in contrast to the voltage-gated Cl– enters channels responsible for the action potential and the In the case of increased PK+, more positive charges leave Ca2+ influx into the synaptic knob. the cell via K+ efflux, leaving more negative charges behind on the inside. Inhibitory Postsynaptic Potential— the combination of a chemical messenger with its receptor site increases the permeability of the subsynaptic membrane to either K+ or Cl− by altering these ions’ respective channel conformations Neuromuscular Synapses Figure X. Structure and function of a single synapse. Neuron-to-Neuron Synapses Excitatory Synapses allow postsynaptic neuron to create a graded potential which depolarizes the postsynaptic neuron ○ Resting membrane potential becomes less negative Excitatory Postsynaptic Potential— the response to the binding of neurotransmitter to the receptor-channel is Terminates at a muscle cell Neurons will have several collaterals– terminal branches/axon terminals ○ Each of these axon terminals will be innervating one muscle cell Remember that muscle will be composed of several muscle cells and muscle tissue will be composed of many muscle cells Neuromuscular junction Motor end plate— depression where the axon terminal innervates the muscle cell ○ specialized portion of the muscle cell membrane immediately under the terminal button(axon terminal is enlarged into a knoblike structure) CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 5 Figure X. Motor neuron innervating skeletal muscle cells. When a motor neuron reaches a skeletal muscle, it divides into many terminal branches, each of which forms a neuromuscular junction with a single muscle cell (muscle fiber). Figure X. Events at a neuromuscular junction. Neurotransmitters Some common neurotransmitters ○ Acetylcholine ○ Dopamine ○ Norepinephrine ○ Epinephrine ○ Serotonin ○ Histamine ○ Glycine ○ Glutamate Aspartate Gamma-aminobutyric acid (GABA) JA N A H A N G EL IK A EVENTS IN NEUROMUSCULAR JUNCTION 1. An action potential in a motor neuron is propagated to the axon terminal (terminal bouton). 2. This local action potential triggers the opening of voltage-gated Ca2+ channels and the subsequent entry of Ca2+ into the terminal button. ○ Ca2+ is higher outside the cell 3. Ca2+ triggers the release of acetylcholine (ACh) by exocytosis from a portion of the vesicles. 4. ACh diffuses across the space separating the nerve and muscle cells and binds with receptor-channels specific for it on the motor end plate of the muscle cell membrane. 5. This binding brings about the opening of these nonspecific cation channels, leading to a relatively large movement of Na+ into the muscle cell compared to a smaller movement of K+ outward. ○ Acetylcholine–gated receptor channels are nonspecific cation gates also allow entry of Na+(thicker arrow) and exit of K+(thinner arrow) 6. The result is an end-plate potential. Local current flow occurs between the depolarized end plate and the adjacent membrane. ○ In neuromuscular junctions, motor end plates do not have threshold potential. ○ Depolarization on the specific end plate → local current flow 7. This local current flow opens voltage-gated Na+ channels in the adjacent membrane. 8. The resultant Na+ entry reduces the potential to threshold, initiating an action potential, which is propagated throughout the muscle fiber. 9. ACh is subsequently destroyed by acetylcholinesterase, an enzyme located on the motor end-plate membrane, terminating the muscle cell’s response. ○ Binding of Ach is continuous(reversible; may bind again to the receptor) → more entry of Na+ ions ○ As this process is repeated, more and more ACh is inactivated until it has been virtually removed from the cleft within a few milliseconds after its release. ○ Acetylcholinesterases are just attached to receptors ○ Potential manifestation of undegraded Ach is muscle spasm (A buildup of acetylcholine in the synapse paralyzes muscles, which can lead to death.) A N TO N IO LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY [TIMESTAMP 52:30] Classical Neurotransmitters and Neuropeptides content Neuronal Integration Content Figure X. Determination of the grand postsynaptic potential by the sum of activity in the presynaptic inputs. Two excitatory (Ex1 and Ex2) and one inhibitory (In1) presynaptic inputs terminate on this hypothetical postsynaptic neuron. The potential of the postsynaptic neuron is being recorded. For simplicity in the fi gure, summation of two EPSPs brings the postsynaptic neuron to threshold, but in reality, many EPSPs must sum to reach threshold. Presynaptic Inhibition Content Figure X. Presynaptic inhibition. A, an excitatory terminal ending on postsynaptic cell C, is itself innervated by inhibitory terminal B. Stimulation of terminal A alone produces an EPSP in cell C, but simultaneous stimulation of terminal B prevents the release of excitatory neurotransmitt er from terminal A. Consequently, no EPSP is produced in cell C despite the fact that terminal A has been stimulated. Such presynaptic inhibition selectively depresses activity from terminal A without suppressing any other excitatory input to cell C. Stimulation of excitatory terminal D produces an EPSP in cell C even though inhibitory terminal B is simultaneously stimulated because terminal B only inhibits terminal A. CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 6 LECTURE 2 - NEURONAL PHYSIOLOGY | ANIMAL PHYSIOLOGY V. Neural Signaling and External Agents Neural Signaling and External Agents JA N A H A N G EL IK A Possible actions? ○ Alter neurotransmitter properties ○ Modify interactions ○ Influence reuptake or destruction ○ Replace neurotransmitter Synthetic and natural toxins can alter resting potentials and action potentials ○ Tetraethylammonium (TEA) Selectively blocks most types of gated K+ channels when placed at either the ICF or ECF Initially used as a vasodilator and antihypertensive Several fatal reactions Side effects during overdose (e.g., arrhythmia) ○ Ouabain A plant poison that stops the Na+ /K+ pump ○ Conotoxins ○ Tetrodotoxin Specific for voltage-gated Na+ channels and binds to the extracellular region of the channel If injected inside the neuron, TTX has no effect on action potential propagation, demonstrating that TTX is specific in blocking the entry of Na ○ Ethanol ○ Cocaine Blocks reuptake of the neurotransmitter dopamine at presynaptic terminals by competitively binding with the dopamine reuptake transporter o Continuous action potential brought by dopamine stuck in the synaptic cleft brings the feeling of fulfillment ○ Strychnine ○ Tetanus toxin Prevents release of inhibitory transmitter, gamma-aminobutyric acid (GABA), from inhibitory presynaptic inputs terminating on neurons that supply skeletal muscles A N TO N IO CDC UNIVERSITY OF THE PHILIPPINES BAGUI O 7