FINAL REVIEW❗️ 2 PDF

1 - HOMEOSTASIS Regulation - continuous and actively responsive to Physiology is the study of how the body functions and...

1 - HOMEOSTASIS Regulation - continuous and actively responsive to Physiology is the study of how the body functions and changes emphasizes how the body maintains itself. Function and integration - how parts of the body **need 3.5 ml/kg/min O2 to live work together at various levels of organization and in the entire organism Chemical messengers Hormones - target cells in one/more distant places Organ systems - 11 (NIICER DRUMS) · ○ Target cells in close proximity to site of paracrine Nervous, Integumentary, Immune, Circulatory, release of paracrine substance Endocrine, Respiratory, Digestive, Reproductive, Neurotransmitters - neuron/effector cell in close Urinary, Musculoskeletal, and Skeletal. Cutocine proximity to site of neurotransmitter release ○ Autocrine substance acts on same cell Body Fluid Compartments: that secretes the substance INTRACELLULAR - 67% of body fluid ○ High K+ Circadian rhythm EXTRACELLULAR Controlled by suprachiasmatic nucleus in ○ Plasma - 25% of ECF, 7% of body fluid hypothalamus ○ Interstitial fluid - 75% of ECF, 26% of Sleep needed to lower blood pressure body fluid Melatonin secreted by pineal gland ○ High Na+ and Cl- Separated by a selectively permeable membrane ○ Results in chemical disequilibrium Receptors detect changes in the environment. Effectors carry out the necessary responses. Feedback Systems counteract (negative feedback) or enhance (positive feedback) the stimulus General Adaptation Syndrome (GAS) - Hans Selye Alarm reaction - initial response to stress E Positive feedback > amplifying - ○ Attempt to restore homeostasis When you want something to end Resistance development - improve capacity-build f Accelerates a process Clotting process to seal wound reserves Exhaustion - system breaks down Homeostasis is the body’s ability to maintain a stable internal 2X: environment despite external changes. childbirth Fight or flight - releasing adrenaline, cortisol, etc. 3 states of total-body balance Dynamic consistency - levels change over short Negative balance - loss>gain periods of time but remain relatively constant over Positive balance - gain>loss long periods Stable balance - gain=loss Accomplished most often by negative feedback loops 2 - CHEMICAL COMPOSITION Homeostasis ≠ equilibrium Essential chemical elements in the body Normal pH = 7.4 Major (4) - 99.3% of total body atoms ○ Hydrogen (63%) E BEHAVIOURAL - learned over time ○ Oxygen (26%) Stomping and clapping to increase blood flow ○ Carbon (9%) ○ Nitrogen (1%) PHYSIOLOGICAL - vasoconstriction to decrease heat loss in Mineral (7) - 0.7% of total body atoms body stabilizes Trace (13) - less than 0.01% of total body atoms > - Negative feedback - going back to set point > most common - Molecular shape - rotation around different C-C bonds allows Enzymes - proteins Feedforward - anticipates change before it occurs different molecular shapes to form Active product - controls sequence of chemical rxns by inhibiting the rate-limiting enzyme Control vs regulation Control - fixed setting without continuous Amphipathic - molecule having both hydrophilic and adjustments hydrophobic parts  Polar regions at the surface Minerals - used as cofactors and in a wide range of processes ○ Stores/releases calcium Nonpolar regions toward center Golgi apparatus - cup-shaped sacs located near the Basal and resting metabolism nucleus Classes of organic molecules Basal metabolic rate (BMR) - measure of amount of ○ Concentrates, modifies, sorts proteins Carbohydrates - 1% body weight energy per unit of time necessary to keep the body from rough ER ○ Disaccharides alive at complete rest Mitochondrion - rod/oval-shaped surrounded by 2 ○ Polysaccharides ~3.5 ml of O2/kg/min membranes, inner membranes fold and form cristae Lipids - 15% body weight For every litre of O2 used, 5 kcals are released ○ Major site of ATP production, O2 ○ Triglycerides utilization, and CO2 formation ○ Phospholipids majority of body 3 - CELLS ○ Steroids weight Embryogenesis - processes leading to the development of an Lynn Margulis - Endosymbiotic Theory Proteins - 17% body weight a embryo from an egg Originated as prokaryotic endosymbionts which ○ Polypeptides came to live inside eukaryotic cells Nucleic acids - 2% body weight ○ Derived from bacteria (might bear ○ DNA bacterial molecular motifs) ○ RNA Apoptosis (programmed cell death) pH Membrane blebbing Normal pH = 7.4 Nuclear breakdown Acidic - less than 7 Chromosomal fragmentation Basic - greater than 7 Bundling of cellular contents into apoptotic bodies - marked for phagocytosis Active process (ATP) **to lose 1lb of body fat, must expend ~3500 kcals 1lb muscle requires 35 kcals per day to maintain Nonessential amino acids - Arginine Spherical cell enlargement E - - - Cysteine Glutamine Tyrosine Surface area - increases by square of cell’s size Volume - increases by cube of cell’s size **different for muscle fibres 3 classes of cytoskeletal filaments Actin - 7 nm E Major proteins + functions Plasma membrane ○ Composed of G-actin (globular actin) Regulate gene expression - make RNA/DNA, Cholesterol content of RBC increases = membrane ○ Twists into F-actin (filamentous actin) synthesize polypeptides fluidity decreases (lipid shell stiffens) Intermediate - 10 nm Transporter - mediate movement of solutes across Fluid-mosaic model - mixture of membrane proteins ○ Composed of proteins (keratin, desmin, plasma membrane can move within the lipid bilayer lamin) Enzymes - accelerate chemical rxns Microtubule - 25 nm Cell signaling - enable cells to communicate 3 types of specialized membrane junctions ○ Composed of tubulin Motor - initiate movement - Desmosome - region between 2 adjacent cells Structural - support, connect, strengthen Defense - protect against infection/disease E - - Tight junction - plasma membranes join so that no extracellular space remains Gap junction - protein channels that link cytosols Transcription to translation Stress can be: Protein interactions Genomic or nongenomic Structural - collagen fibres in CT, keratin in skin Cell organelles Long term or short term Enzymes - assist chemical processes Nucleus - largest, no membrane-bound organelles Antibodies - part of immune system ○ Stores and transmits genetic info (DNA) Transcription Receptors - receive signals Nucleolus - densely stained filamentous structure Occurs in nucleus Membrane transporters - across cell membranes within nucleus DNA to mRNA Regulatory proteins - transcription factors ○ Site of ribosomal RNA synthesis Codons = mRNA triplets Binding proteins - hemoglobin + O2, hormones + BP Rough ER - flattened sacs enclosing a space that is ○ 64 three-letter combinations Signal molecules - imparts a change continuous ○ Only 61/64 are used to specify amino ○ Synthesized proteins enter then are acids Vitamins - serve as coenzymes or perform a specific function distributed ○ 3/64 are stop signals 2 classes: Smooth ER - highly branched tubular network that Uses a promoter to turn gene transcription on/off ○ Fat-soluble - A, D, E, K does not have ribosomes Exons = expressing regions ○ Water-soluble - B, C ○ Contains enzymes for fatty acid/steroid Introns = intervening sequences, non-coding synthesis  remove introns - Spliceosomes = remove non-coding portions from If solutes can cross the membrane, tonicity will mRNA change Plasma has the same osmolality as 0.3m glucose or Translation 0.15 NaCL solution Occurs in cytoplasm ○ Considered isosmotic mRNA to protein (amino acids) No net movement of water = isotonic 3 stages: ○ Initiation > assembly of ribosome E - ○ Elongation > adding AA to polypeptide - chain ○ Termination > release of protein - Pathways for glycogen synthesis and storage Glucose to other tissues = hexokinase water out Glucose to liver = phosphatase water in Chigh solute outside (high solute inside Oxidative deamination - removing an amino group Ions Oxidative transamination - transferring an amino group Movement influenced by electrical gradients ○ Attracted by opposite charges 4 - SOLUTES AND WATER Diffusion > solute - Lipophilic molecules Passive Move by simple diffusion across lipids Facilitated diffusion > NO ATP required for polar - , molecules Rate dependent on solubility of lipids ○ High to low concentration (glucose ions) , Proportional to surface area of membrane Primary and secondary active transport > requires ATP Na/k pump - , Fick’s Law A single gene (sickle-shaped RBC) ○ Low to high concentration Movement until equilibrium Voltage-gated ion channels (VGICs) Sickle cell anemia caused by single nucleotide Directly related to temperature Play crucial roles in excitable (neuronal and muscle) polymorphisms (SNP) aka a stop Inversely related to molecular weight/size cells One base pair change (glutamine to valine) Open system Allow a rapid and coordinated change in membrane Flux = amount of substance that crosses a surface in potential when triggered A single gene (myostatin) a unit of time Transmembrane proteins that create electrical Myostatin is a negative regulator of muscle growth Nonpolar molecules diffuse rapidly signal Amino acid sequence of myostatin in ○ Polar molecules do not ACTIVE need ATP **cell is more permeable to K+ than Na+ double-muscled cattle has a premature stop codon = at amino acid 228 = makes protein non functional PASSIVE = No ATP Osmosis => PASSIVE Protein binding Movement of water from low -> high concentration Increasing ligand concentration increases percent Diffusion of solvent saturation Aided by channels called aquaporins > allows water - to more rapidly ○ Found in kidneys, eyes, lungs, salivary Substrate concentration glands, and brain For a given amount of enzyme, the rxn rate Requirements: increases until there is more substrate than enzyme ○ Solute concentration difference on either Eventually reaches a plateau (saturation) E○ side Membrane must be impermeable to Metabolic pathways to produce ATP solute Glycolysis - anaerobic respiration 2 ATP 2 NADH = ○ **solutes that cannot cross are called osmotically active , ○ Occurs in cytoplasm Krebs - aerobic 2 ATP + FADH2 and NADH -> CO2 by product , ○ Occurs in mitochondria (matrix) Tonicity Oxidative phosphorylation (ETC) - aerobic Volume change of a cell Secondary active transport > uses energy in electrochemical gradient - ○ Occurs in mitochondria (inner membrane) Depends on concentration of nonpenetrating Cotransport - symport, when solutes move in the solutes same direction It pumped = proton gradient & 2 final electron acceptor > - forms water  Countertransport - antiport, when solutes move in ○ Specificity, affinity, competition, Structure of skeletal muscles opposite directions saturation CT components Uses electrochemical gradient as its energy source Surrounded by epimysium > covers entire muscle - Resting membrane potential Antagonistic control - uses different signals to send a Perimysium divides muscle into fascicles (group of Membrane potential less than negative = parameter in opposite direction fibres) ↳ covers each fascicle depolarization Example: heart rate Each fascicle divided into myofibrils surrounded by Membrane potential greater than negative = ○ Sympathetic neuron speeds it up endomysium > covers myofibrils - hyperpolarization ○ Parasympathetic neuron slows it down Endocytosis and exocytosis Receptor specificity 3 types of endocytosis: Cells express different receptors Pinocytosis - fluid "cell drinking" Response is based on cell type, intracellular E Phagocytosis - bacteria/large particles "cell eating" Receptor-mediated - specific molecules that must signaling cascade coupling, and other simultaneous signals being received bind to receptors Cyclic AMP second-messenger system (cAMP) Relays signals to inside of cell Allows for activation of enzymes, proteins, and Myofibrils - A band (dark), I band (light) metabolic pathways Thick filament - myosin SECOND MESSENGERS : ○ Structural ↳ large molecules into ↳ materials out of Receptor agonists and antagonists > relay signals from surface ○ Has ATPase cell membrane cell (NT , hormones, Primary ligand activates a receptor to target Thin filament - actin waste ? Agonist also activates receptor > cAMP Ca IP DAG ○ Globular or fibrous Has tropomyosin and troponin , ○. , Antagonist blocks receptor activity Troponin I (inhibitory) Troponin T (tropomyosin) 6 - SKELETAL MUSCLE Troponin C (Ca) Muscle contraction **no ATP = actin and myosin stay bound = rigor CNS to PNS Afferent (sensory) Sarcomere Efferent 5 - CELL SIGNALING ○ Somatic Relaxed = 2.6u Cell-to-cell communication Contract = 1.6u ○ Autonomic (sympathetic and Electrical signals Titin is the largest protein in the body parasympathetic) ○ Changes in membrane potential ○ Nervous system 3 types of muscles Chemical signals Skeletal - large, multinucleate cells ○ ○ Secreted by cells into ECF Ligands E Cardiac - smaller, branches, uninucleate Smooth - small and lack striations ○ Endocrine system ○ In arterioles Target cells respond to signals ○ Target response depends on target receptor Sarcoplasmic reticulum - storage for Ca SKELETAL ○ Example: blood vessels constrict/dilate depending on receptor type Motor unit - motor neuron and all the fibres it innervates How much you decide to recruit will determine force More motor units = more fibres = more cross CARDIAC bridges = more force Contraction ≄ shortening ↳ ○ Refers to activation of cross-bridges Neuromuscular junction - junction of an axon terminal with motor end plate SMOOTH All neuromuscular junctions are excitatory Contains acetylcholinesterase - breaks down ACh Alpha motor neurons - innervate skeletal muscle Protein binding of chemical signals ○ Found in brainstem and spinal cord ○ Myelinated - insulated (fat)  Acetylcholine - neurotransmitter Length-tension relationship > force depends on initial length - Titin - responsible for most of passive elastic properties of relaxed fibres Disruption of neuromuscular signaling Increased stretch = passive tension increases active decreases Curare - poison which binds to nicotinic ACh ○ Due to elongation of titin filaments receptors Active tension altered by changing length of the ○ Causes death by asphyxiation fibre Drugs that block neuromuscular transmission (for ○ Optimal length surgical procedures) > - CT activ 3 myosin ○ Succinylcholine > - ○ Rocuronium ○ Vecuronium Bacterium clostridium botulinum blocks release of ACh ○ Produces botulism (food poisoning) Excitation-contraction coupling - sequence of events where an AP causes cross bridge formation/contraction of the muscle AP conduct messages through T-tubules > EXCITATION 4 stages of a cross-bridge cycle E - Initiate Ca release > CONTRACTION - 1) Cross-bridge binds to actin S Ca binds to troponin = sliding filament theory > COUPLING - 2) Cross-bridge moves Ca releases from SR 3) ATP binds to myosin = cross-bridge detaches ATPase pumps return Ca ions to SR by active No ATP = rigor mortis transport 4) Hydrolysis of ATP energizes cross-bridge ○ Leads to decreased Ca around actin and 3 ways a muscle fibre can form ATP myosin = muscle relaxation Phosphorylation of ADP by creatine phosphate Force velocity curve Oxidative phosphorylation of ADP in mitochondria At any given velocity, the trained can apply more Cytosolic increase in Ca Phosphorylation of ADP by glycolytic pathway in force Dihydropyridine (DHP) receptor - voltage sensor cytosol Against any given load, the trained can move faster Ryanodine receptor - protein in SR, forms Ca channel Functions of ATP in a muscle contraction During T-tubule AP, amino acid residues within DHP Na-K-ATPase: maintains Na and K gradients CONCENTRIC Ca-ATPase: energy for active transport of Ca into receptor induce a conformational change ○ Pulls open ryanodine channel ↑ velocity - ↓ force reticulum, allows muscle to relax ○ Ca released from terminal cisternae into myosin-ATPase: energizes cross-bridges, energy for cytosol ECCENTRIC force generation Binding of ATP to myosin dissociates cross-bridges interactions between myosin and activ ↓ velocity ↑ force bound to actin = > - Cross-bridge cycling Length of filaments don’t change = only slide Sequence of events: AP to muscle contraction Relaxed = low cytosolic Ca 1. AP initiated and propagated to axon terminals ○ Cross-bridge cannot bind to actin Enters through voltage-gated Ca Activated = high cytosolic Ca channels ○ Cross-bridge binding sites exposed Triggers release of ACh ○ Binds to actin and generates force 2. ACh diffuses from terminals to motor end plate Conformational change - propels thin filaments 3. ACh binds to nicotinic receptors toward center of sarcomere Increases permeability to Na and K 4. More Na moves into fibre than K moves out Sliding filament theory Depolarization and end-plate potential Relaxed to shortened (thick and thin filaments (EPP) > graded potential - overlap) tension increases with frequency 5. Depolarizes until threshold potential Frequency-tension relationship > - ○ A band unchanged Generates AP along T-tubules Single AP lasts 1-2ms, twitch may last for 100ms or E ○ ○ I band reduced H zone reduced more Second AP is possible 6. AP in T-tubules induces DHP receptors to pull open ryanodine receptor channels Releases Ca from terminal cisternae Summation - increase in muscle tension from 7. Ca binds to troponin, causing tropomyosin to move successive APs during mechanical activity phase away Tetanus - maintained contraction in response to 8. Energized myosin cross-bridges bind to actin E repetitive stimulation very high frequencies  9. Cross-bridge binding triggers release of ATP Type I: slow-oxidative fibres Rates to reach maximum tension 10. ATP binds to myosin, breaking link between actin E Type IIa: fast-oxidative glycolytic fibres Type IIx: fast-glycolytic fibres Myosin in each fibre determines maximal rate of and myosin = cross-bridges dissociate cross-bridge cycling and maximal shortening velocity Oxidative - numerous mitochondria, high capacity 11. ATP bound to myosin is split, energizing myosin for oxidative phosphorylation cross-bridge ○ Aka red muscle fibres Glycolytic - few mitochondria, high concentration of glycolytic enzymes Control of muscle tension 12. Cross-bridges repeat last 4 steps, producing sliding Depends on 2 factors: ○ Allows for quick bursts filament theory Amount of tension developed by each fibre ○ Aka white muscle fibres Continue as long as Ca remains bound to - ala tetanus E Number of fibres contracting troponin Tetanic muscle tension - results from successive recruitment of 13. Cytosolic Ca concentration decreases as Ca-ATPase Control of shortening velocity the 3 types of motor units > muscle has no time to relax actively transports Ca into SR - Depends on: 14. Removal of Ca from troponin, cross-bridge cycle Load on muscle ceases, muscle relaxes E Types of motor units Number of motor units recruited Single fibre contraction Tension - force exerted on an object by a Atrophy contracting muscle Disuse - arm in a cast Load - force exerted on muscle by an object Denervation - loss of function * **Tension and load are opposing forces Twitch - mechanical response of a fibre to a single Muscle disorders AP Muscle cramp Isotonic twitch Latent period - time from AP to onset of contraction E Overuse (DOMS, rhabdomyolysis) Disuse leads to atrophy Inherited disorders ○ Delay due to excitation-contraction ○ Duchenne muscular dystrophy coupling ○ McArdle’s disease Fast-twitch and slow-twitch muscles Contraction time - from beginning of tension Slow-twitch - large amounts of red myoglobin, development to peak tension Contraction types numerous mitochondria, and extensive blood Relaxation time - from peak tension until tension Isometric (constant length) - load is greater than supply declines back to 0 tension developed by muscle ○ Fatigue resistant Isotonic (constant tension) Rate of fatigue development in 3 fibre types ○ Shortening (concentric) - tension>load ○ Lengthening (eccentric) - load>tension Muscle damage and repair Satellite cells (SCs) - stem cells near muscle fibres Divide and fuses to: ○ Damaged muscle cells (repair) ○ Each other to form new fibres Fast-twitch - large diameter, pale colour ○ Easily fatigued  When a fibre is damaged… Antibodies block nicotinic ACh receptors in Satellite cell activated - triggers proliferation postsynaptic membranes ○ Cells multiply - Produces muscle weakness (eyes, eyelids, face) Some cells return to resting state Neostigmine blocks the enzyme that degrades ACh Remaining cells move toward the damaged muscle fibre - chemotaxis Cause of muscle fatigue Cells fuse with damaged fibre and repair it by Decrease in ATP adding new nuclei - hypertrophy Increase in ADP, Pi, Mg, H Some cells fuse together to form completely new Central command fatigue - regions of cerebral fibres - hyperplasia cortex fail to send excitatory signals to motor After this process, a regenerated muscle fibre is neurons ready to function again ○ Cause person to stop exercising even when muscles are not fatigued 3 classes of neurons 7 - NEURONAL SIGNALING Interneurons - integrators and signal changers & Neuron ○ Integrate afferent and efferent neurons Dendrites - receives info and sends to soma into reflex circuits & Soma - aka cell body ○ Entirely within CNS ○ Contains nucleus and ribosomes ○ >99% of all neurons Axon - carries signals to target cells Afferent - transmit info from receptors Axon hillock - generates AP ○ Splits into long peripheral process in PNS Axon terminals - releases NT and short central process in CNS Schwann cells - form myelin sheath Efferent - transmit info out of CNS to effector cells Myelin sheath - speeds up conduction of electrical (muscles, glands, etc.) signals ○ Small segment of axon in CNS, most in Nodes of ranvier - gap between regions of myelin PNS sheath ○ Permit exchange of Na and K f Creatine kinase > energy production - Glial cells Aka creatine phosphokinase (CPK) Provide neurons with physical and metabolic ↑C damage Myelinated nerve transmission = Aid diagnosis of myocardial infarction, muscular support 100 m/sec (360 km/hr) dystrophy, rhabdomyolysis, etc. Astrocytes - regulate composition of ECF Human eye blinks at 100-400ms S Rhabdomyolysis - muscle damage producing ○ Removes K and neurotransmitters weakness and pain around synapses Synapses Isoenzymatic forms of CK Microglia - specialized, macrophage-like Electrical ○ CK-MM isoenzyme - released by ○ Perform immune functions Chemical damaged skeletal muscles ○ Synapse remodeling and plasticity Inhibitory ○ CK-MB isoenzyme - released by damaged Ependymal - line fluid-filled cavities Excitatory heart muscle ○ Regulate production/flow of cerebrospinal fluid Action and graded potentials Hypocalcemic tetany Oligodendrocytes - form myelin sheath More than 40 neurotransmitters in nervous system Involuntary tetanic contraction of skeletal muscles Examples: ACh, norepinephrine, dopamine, Growth and development of neurons gamma-aminobutyric acid (GABA), glutamate, Duchenne muscular dystrophy Begins with stem cells that can develop into serotonin, histamine Most severe neurons or glia Caused by mutations in a recessive gene located on Growth cone - specialized enlargement, forms tip of Axonal transport the X chromosome each axon Movement between soma and axon terminals ○ Codes for a protein called dystrophin ○ Once target of growth cone is reached, Proceeds with the help of motor proteins: ○ Located under sarcolemma where it synapses form Kenesins - move materials forward provides support by bridging Plasticity - ability to modify structure/function in ○ Anterograde transport cytoskeleton and myofibrils response to stimulation/injury ○ Nutrients, synaptic vesicles, Mutations result in damage to sarcolemma that ○ Varies with age mitochondria cannot be repaired by satellite cells Dyneins - move materials backward ○ Causes necrosis and replacement by Regeneration of axons ○ Retrograde transport fibrous CT and fatty tissue necrosis-death of cells Can repair themselves if damage occurs outside ○ Recycled growth factors, pathogens CNS and if neuron’s cell body is unaffected Myasthenia gravis After injury, separated axon segment degenerates Autoimmune disease  ○ Part still attached gives rise to a growth Leakage of charge (K) across membrane reduces cone local current at sites farther along the membrane Return of function after a peripheral nerve injury is Summation - addition of graded potentials from delayed several stimuli ○ Axon regrowth proceeds at a rate of only 1mm/day Action potential Spinal injuries crush the tissue, leaving axons intact Brief all-or-none depolarization of membrane ○ Apoptosis of oligodendrocytes = loss of ○ Very rapid (1-4ms) myelin sheath Reverses polarity in neurons Severed axons within CNS may grow small Conducted without decrement extensions but no significant regeneration Occurs in trigger zone through axon Voltage-gated ion channels Membrane potential Depolarization - moving from RMP to less negative Voltage difference between in/out a cell values Overshoot - inside becomes more positive than Resting membrane potential outside Potential difference across plasma membrane when Repolarization - returning to RMP at rest Hyperpolarization - potential becomes more How neurotransmitters work ○ Exists due to excess of negative ions negative than RMP Nerve impulse stimulates release of inside and excess of positive outside neurotransmitters from vesicles ○ Inside = negatively charged Electrical synapse Increased frequency of stimulation = increased NT ○ Outside = positively charged Plasma membranes of pre/postsynaptic cells joined Typically -40 to -90 mV by gap junctions Change in potential due to movement of ions Electrical activity of presynaptic neuron affects Na/K ATPase pump establishes concentration electrical activity of postsynaptic gradients = keeps resting potential at -70 mV Equilibrium potentials Voltage difference across a membrane Nernst equation: based on ion concentrations K = -90mV Na = +66 mV Graded potentials Potential change of a variable amplitude and Removal of NT duration that is conducted decrementally ○ ↳ Potential change decreases as distance Reuptake - active transport back to presynaptic terminal for reuse from site increases Transport into nearby glial cells = degraded From ligand-gated and mechanically-gated Diffusion away from receptor site channels Chemical synapse Enzymatic transformation into inactive substances No threshold/refractory period Presynaptic neurons release NT and they bind to Occurs in dendrites and cell body receptors on postsynaptic neurons Excitatory postsynaptic potential (EPSP) - asparate glutamate Goes close to threshold , Process: 1) AP reaches terminal Depolarization E 2) Voltage-gated Ca channels open 3) Ca enters terminal 4) Neurotransmitter released and diffuses into cleft 5) Neurotransmitter binds to postsynaptic receptors 6) Neurotransmitter removed from synaptic cleft Inhibitory postsynaptic potential (IPSP) > - glycine. GABA ○ Leads to excess muscle contraction and Goes away from threshold rigid/spastic paralysis hyperpolarization Clostridium botulinum bacilli causes botulism ○ Reduced muscle contraction and flaccid paralysis Botulinum toxin or botox Amino acid neurotransmitters Most common NT in the CNS Excitatory - aspartate, glutamate Inhibitory - glycine, GABA Glutamate Primary NT of excitatory synapses Positive feedback - opens Na channels 2 types: metabotropic, ionotropic Negative feedback - opens K channels Long-term potentiation (LTP) - couples frequent activity across a synapse with lasting changes Myelination and saltatory conduction of AP Axo-axonic synapse ○ Cellular process involved in learning and Myelin is an electrical insulator Axodendritic memory ○ Adds speed, reduces metabolic cost, Axosomatic saves room in NS GABA1 ○ Makes it difficult for charge to blow Gamma-aminobutyric acid - major inhibitory NT in between ECF and ICF brain APs occur only at nodes of ranvier where myelin Small interneurons that dampen activity coating is interrupted Ionotropic receptor increases Cl flux into cell ○ Na channels are high ○ Results in hyperpolarization Saltatory conduction - APs jump from one node to the next GABA2 Has several binding sites for other compounds Absolute and relative refractory periods of AP (steroids, etc.) Absolute - no stimulus can trigger another AP Ethanol stimulates GABA synapses and inhibits ○ Occurs when Na channels are either glutamate synapses already open or have proceeded to inactivated state Glycine Relative - larger than normal stimulus can initiate a Major inhibitory NT in spinal cord and brainstem new AP Essential for maintaining balance of excitatory and ○ Can last as long as 15ms inhibitory activity in spinal cord ○ Coincides with period after Process of action potential Strychnine - antagonist hyperpolarization 1) Resting membrane potential ○ Leads to convulsions, spastic contraction E Depolarizing stimulus of muscles, death 2) Membrane depolarizes to threshold Voltage-gated Na and K channels open Neuromodulators 3) Rapid Na entry depolarizes cell Modify postsynaptic cell’s response to specific 4) Na channels close neurotransmitters 5) K moves from cell to ECF May change synthesis, release, reuptake, or 6) K channels remain open and additional K leaves metabolism of a NT Hyperpolarization Associated with slower events (learning, 7) Voltage-gated K channels close development, motivational states) 8) Cell returns to resting membrane potential Serotonin - has an excitatory effect on muscle control pathways, inhibitory effect that mediate sensations ○ 90% found in digestive, 8% in blood platelets and immune cells, 1-2% in brain ○ Selective serotonin reuptake inhibitors (SSRIs) - aid in treatment of depression ○ Diethylamide (LSD) - causes intense Diseases affecting synaptic mechanisms visual hallucinations Clostridium tetani produces tetanus toxin Acetylcholine (ACh) Clusters of cell bodies = nuclei White matter Major NT in the PNS (neuromuscular junctions) and Dendrites Interior CNS (brain) Axon terminals Bundles of fibres connecting regions of brain Cholinergic neurons - release ACh White matter: ACh binds to muscarinic or nicotinic receptors Myelinated axons Layers of gray matter superficial Synthesized in cytoplasm of terminals and stores in Glial cells Molecular & vesicles Axon bundles = tracts External granular Degradation occurs via acetylcholinesterase ○ Very few cell bodies External pyramidal ○ Nerve gas Sarin inhibit Internal granular acetylcholi