E109 Lecture 4: Nervous System II Fall 2024 PDF

Lectures 3+4 Learn about graded potentials, myelination, and saltatory conduction Observe that the cell body of a neuron functions as an integrating center Learn that the strength of the graded potential produced by presynaptic neurons dissipates in the cell bod...

Lectures 3+4 Learn about graded potentials, myelination, and saltatory conduction Observe that the cell body of a neuron functions as an integrating center Learn that the strength of the graded potential produced by presynaptic neurons dissipates in the cell body; axon hillock is a key “trigger” point for action potentials Understand that graded potentials entering the cell body may be excitatory (+) or inhibitory (-) Appreciate that the sum of the graded potentials in the cell body determine whether an action potential will fire Refractory Periods Both Na+ Both channels channels Na+ channels close and Na+ channels reset to original position closed open channels K+ channels open while K+ channels remain open closed Na+ Na+ and K+ channels K+ K+ K+ Absolute refractory period Relative refractory period Membrane potential (mV) Action potential actionpotentials alwayslookthesame miliseconds cancomeevery 4 Ion permeability Na+ K+ High High Excitability Increasing Zero Time (msec) Propagation Rates/Graded potentials The rate of action potential propagation depends on the resistance of the axon to current loss charge disapates as It moves away from point of origin Increased resistance to current loss across the membrane Amplitude of graded maintains signal strength over potential (mV) longer distance Distance Distance Stimulus point of origin Propagation Rates humans have less charge loss by insulation of my in Speed of action potential in neuron influenced by Diameter of axon Larger axons are faster Resistance of axon membrane to ion leakage out of the cell Myelinated axons are faster Schwann cells Saltatory Conduction voltage gated channels where no Mccleary new graded potential is generated Myelin Degeneration Myelin degeneration can result in significant loss of function Diseases: Multiple Sclerosis, Meylitis, Leukodystrophy action potentialdisaptes isnt strongenough to reach w out my in sheath Review Ion concentration gradients and membrane permeability determine membrane potential in cells Dynamic changes in membrane permeability (Na+ & K+) cause the development of an action potential Action potentials are triggered by local current flow (a graded potential) The strength of graded potentials depends on resistance to current flow Myelination increase the speed of AP propagation E109 Lecture 4: Nervous System II Graded vs. Action potential !"#$%&'()* ")+,#-.)*(/,$+)0 Graded vs. Action potential !"#$%&'()*1%0-#-.)* (/,$+)0 Graded vs. Action potential makes't Graded Potentials Distance Stimulus point Distance of origin gradedpotentialslead to action potentials Action Potentials Graded Potentials all or none no threshold Na+ and K+ Na+, K+, Ca2+, Cl- voltage gated voltage, ligand, mechanically gated depolarizing depolarizing or hyperpolarizing refractory period no refractory per.; signals can sum Anatomy of the Neuron dendrites Input signal nucleus cell body Integration axon hillock myelin sheath axon Output signal post-synaptic neuron Figure 8-2 Input signal Input signal Integration Axon hillock Axon (initial segment) Output signal Input signal Input signal Integration Axon hillock Axon (initial segment) Output signal Integration Input signal Integration Axon hillock Output signal Integration: Spatial Summation Presynaptic axon terminal spacial summation graded potentialsallow for summation + + Trigger zone Threshold Action potential Integration: Spatial Summation cancels out thepos charge of the sodium will not reach + + Inhibitory neuron Threshold Trigger zone No action potential Integration: Temporal Summation Integration: Temporal Summation Review: Lecture 4 (Part 1) The cell body of a neuron functions as an integrating center The strength of the graded potential produced by presynaptic neurons dissipates as moves toward the axon hillock (trigger zone) The graded potentials entering the cell body may be excitatory (+) or inhibitory (-) The sum of the graded potentials in the cell body ultimately determine whether an action potential will fire E109 Lecture 4: Nervous System II (Part 2): synapses E109 Lecture 4: Nervous System II Observe that synapses are used for communication between a neuron and another cell Learn that synapses can be electrical or chemical Understand that chemical synapses covert electrical information to chemical information Chemical synapses can be ionotropic or metabotropic Observe that synaptic transmission can be altered by neurotoxins or pharmacological agents Communication by Neurons Input signal how neurons communicate Integration Types of synapses Electrical: Axon hillock found in the CNS, smooth Axon (initial muscle, Cardiac muscle segment) Chemical: most prevalant ionotropic (fast) Output signal metabotropic (slow) Electrical Synapse can pass cell to cell this is electrical synapsis Chemical Synapse more frequent action Axon of presynaptic Axon terminal potential more neuron Mitochondrion neurotransmitters Vesicles with neurotransmitter released Mitochondrion Axon terminal Postsynaptic neuron Synaptic vesicles Synaptic cleft Synaptic cleft Muscle fiber Neurotransmitter Receptors Postsynaptic membrane Events at the Synapse and Exocytosis 1 An action potential depolarizes the axon terminal. The depolarization opens Axon 2 voltage-gated Ca2+ terminal channels and Ca2+ Synaptic enters the cell. vesicle Neurotransmitter molecules 3 Calcium entry triggers exocytosis of synaptic Action vesicle contents. potential depolarized membrane voltage gate 4 Neurotransmitter diffuses across the synaptic cleft cart channels and binds with receptors open 3 on the postsynaptic cell. 1 Neurotransmitter binding Ca2+ 5 initiates a response in Synaptic the postsynaptic cell. Docking cleft protein this space is 2 4 What makes this Receptor synapsis chemical Postsynaptic cell Voltage-gated Ca2+ channel Cell 5 response Synthesis and Recycling of Neurotransmitters example of chemical synap Acetylcholine (ACh) is made Mitochondrion 1 from choline and acetyl CoA. Acetyl CoA CoA 2 In the synaptic cleft ACh is rapidly Axon broken down by the enzyme terminal acetylcholinesterase. Enzyme A Acetylcholine Ch 1 Choline is transported back into A Synaptic 3 the axon terminal by co-transport Ch vesicle 4 with Na+. Ch Recycled choline is used to make 4 A ACh. 3 Ch Na+ Choline Cholinergic Ch 2 receptor A A Ch Acetate Acetylcholinesterase (AChE) Postsynaptic cell breaksthisneurotransmitter dowsfaysoathgtadh.de Irium  ay 9 Chemical Synaptic Diversity changesmetabolism ligand gated channels of cell longerlived Ionotropic Metabotropic caninvolve shortlived opening ion quick response channels 1 but can do a lot more Variation in the Postsynaptic Response Presynaptic axon terminal Slow synaptic potentials Rapid, short-acting Neurotransmitter and long-term effects fast synaptic potential Chemically G protein–coupled gated ion channel receptor Inactive Postsynaptic pathway cell Alters state of Activated second ion channels messenger pathway Ion channels close Modifies existing Ion channels open proteins or regulates synthesis of new proteins More More K+ Less K+ Less Na+ in out or out Na+ in Cl– in EPSP = IPSP = EPSP = Coordinated excitatory inhibitory excitatory intracellular depolarization hyperpolarization depolarization response Synaptic Transmission: possibilities for modulation Many neurotoxins target specific parts of a synapse and disrupt synaptic transmission Botulinum toxin (bacteria) : disrupts vesicle docking Bungarotoxin (sea snakes): binds to and blocks nicotinic ACh receptors Calcicludine (green mamba): blocks voltage gated Ca+2 channels Disruption of synaptic transmission is a symptom of many neurological disorders (depression, schizophrenia, Alzheimer’s, etc.) lack or mutations associated with receptors insufficient neurotransmitter release Review Synapses are used for communication between a neuron and another cell Synapses can be electrical or chemical Chemical synapses covert electrical information to chemical information Chemical synapses can affect the post-synaptic cell through ionotropic or metabotropic pathways Synaptic transmission can be altered by neurotoxins or pharmacological agents E109 Lecture 1: Welcome+Osmolarity, Tonicity, Diffusion Learning Goals Review the syllabus, understand class logistics No “content questions” via email. Use Ed Discussion Individual office hours OK Larc Tutor: Anushka Singh [email protected] Bio Sci Peer Tutors: Gracey Singh [email protected] Alireza Oladaskari [email protected] Understand generally what “physiology” means Learn the difference between osmolarity and tonicity Observe how diffusion works Learn the basics of “Fick’s Law” Understand that there are different types of membrane proteins: some transport ions or molecules, some transmit signals to the cellular environment E109 Lecture 1: Welcome+Osmolarity, Tonicity, Diffusion Human Physiology Human Physiology: The science of the mechanical, physical, and biochemical functions of our bodies Physiology is studied at various levels of organization Important Concept in Physiology: Homeostasis ftp.ffioantiiay around a set point in hot a if workout sweatingafter How to maintain homeostasis Cells contain intracellular fluid (ICF) The cell External membrane Cells ECF environment separates cells from ECF Cells are surrounded by ECF Fluid compartments KEY Intracellular fluid Interstitial fluid Plasma Interstitial Intracellular fluid fluid extra ECF ICF 1/3 2/3 Cell membrane In Maintaining Disequilibrium 160 140 KEY Ion concentration (mmol/L) 0 120 Na K 100 Cl 80 HCO3 Proteins 60 40 20 Intracellular fluid Interstitial fluid Plasma Extracellular Fluid a there is much less k extracellularly thereis much more K  y E109 Lecture 1: Welcome+Osmolarity, Tonicity, Diffusion Osmolarity Number of solute particles per volume A B A B Selectively permeable membrane Less solutes means there is more water osmosis will move water to where there is more solutes to reachequilibrio Osmosis: movement of water across a membrane mum Tonicity MI ions in solution relative to the cell Place Red Blood Cells in solutions with different amounts of solutes Less More solutes solutes 1 iswelling bursts to more solutes on the outside of the cell water is moving water is moving solutes out where the shriveling are bursting Calculating Osmolarity ECF ICF S/V= C extracellularfluid intercellularfluid S= #solutes (mOsm) 300 mOsm/L 300 mOsm/L V= Volume (L) C= solute conc. (mOsm/L) 300 mOsm 600 mOsm S= C x V 1L 2L SECF= 300 mOsm/L x 1L SECF= 300 mOsm in terms of osmolarity FFG ICF must stay in equilibrium to avoid hypotonicity hypertonicity What would happen if you doubled the volume of ECF without changing the number of solutes? it would becomehypotonicrelative to the intercellular fluid dilutedtheECF solutes will try to travel out of the cell to exploding cells  g y Diffusion smaller things diffuse faster Congoredis a much largermolecule KI Congo red Dyes placed in wells of Diffusion of dyes agar plate at time 0 90 minutes later Fick’s law of diffusion If sets upexpectations of howquickly Extracellular fluid things can diffuse Molecular across a Membrane surface area Lipid size Concentration outside cell membrane solubility Factors affecting rate of diffusion through a cell membrane: Lipid solubility Molecular size Concentration Concentration gradient gradient Membrane surface area Composition Composition of lipid layer of lipid layer Intracellular fluid Concentration inside cell Fick’s Law of Diffusion Membrane Permeability Membrane lipid solubility permeability  molecular size Rdiffusion  surface area  conc. gradient  memb. permeability more likely Img ngsare Changing the composition of the lipid layer can increase or decrease membrane permeability. Review Osmolarity- the number of solutes present in a unit volume of fluid. Differences in osmolarity can drive movement of fluids or develop osmotic pressure Tonicity- A physiological feature of a fluid that determines whether fluid will move into or out of cell Diffusion- movement of molecules from an area of high concentration to an area of low concentration. Diffusion across the cell membrane depends on the size of molecules and membrane permeability E109: Membrane Transport & Communication Membrane Proteins Structural proteins communication Enzymes /signaling Membrane receptor proteins Transporters transport – Channel proteins – Carrier proteins E109: Membrane Transport & Communication Learning Goals Finish discussing membrane proteins. Understand symporters, and discuss signal transduction impacting intracellular function. Understand homeostatic control loops To review cellular communication (short & long distance) To understand the classification, structure, and synthesis of hormones To understand hormone interactions To understand the pathways of endocrine regulation Membrane Transporters Facilitated diffusion Equilibrium Conversion can be maintains reached gradient High glucose [Glucose]out  high[Glucose]out concentration [Glucose]in [Glucose]in GLUT stays low ATP ADP G-6-P Glycogen Low glucose concentration Glycolysis I does this maintain to a gradient Co-transport: SGLT Na+ binds to carrier. Glucose binding changes carrier conformation so Na+ Intracellular fluid Lumen of intestine that binding sites now or kidney face the ICF. Na+ [Na+] high SGLT protein Lumen ICF Glu [glucose] low [Na+] low [glucose] high Na+ is released into cytosol, where [Na+] is low. Release changes glucose- binding site to low affinity. Na+ Glucose is released. [Na+] low Na+ binding creates Na+ a high-affinity site for glucose. [glucose] high Lumen ICF Fairies Glu Lumen ICF an or allows sodium tobind give Signaling Pathways: the basic cascade Signal molecule Extracellular signal binds to molecule binds to a cell membrane receptor. Membrane receptor protein Binding activates triggers Intracellular signal molecules Rapid cellular responses alter Target proteins create Response Four Categories of Membrane Receptors Extracellular signal molecules ECF Channel Receptor Receptor Integrin Cell membrane Anchor protein Enzyme G protein Cytoskeleton ICF Receptor- Receptor-enzyme G protein–coupled receptor Integrin receptor channel Ligand binding Ligand binding to a Ligand binding to a G protein– Ligand binding to opens or closes receptor-enzyme activates coupled receptor opens an ion integrin receptors the channel. an intracellular enzyme. channel or alters enzyme activity. alters the cytoskeleton. movement Transduction Pathways Signal Extracellular Signal molecule fluid molecule binds to binds to Membrane receptor initiates Membrane receptor protein Signal transduction by proteins Ion activates channel Amplifier enzymes Intracellular alter signal molecules Second messenger alter molecules Intracellular Target Increase fluid Protein kinases intracellular Ca2+ proteins create Phosphorylated Calcium-binding proteins proteins Response Cell response Review Membrane properties depend not only on the lipid bilayer but the vast array of membrane proteins that regulate transport Membrane proteins serve both a transport and a communication function Signal transduction cascades are initiated by extracellular signals and function to regulate the internal state of the cell E109 Lecture 2: Endocrine Physiology Feedback Regulation S Body Temperature Stimulus Thermoreceptors Sensor Negative Negative feedback feedback loop loop Hypothalamus Integrating Center Sweat Glands Target cells Sweat Secretion Response Heat Loss Local Communication Contact-dependent Autocrine/Paracrine Gap Junctions signals signals Receptor i cells share left cell releases i releases peptide on its cytoplasm Smith to cell own membrane receptor on right then to next cell Local Communication Class concept as a gif Long-distance communication Endocrine System Slower, but longer lasting throughthe bloodstream Blood must travel to get to target cell Endocrine Cell without Cell with peptidehormone will cell receptor receptor onlybe relievedby Target cell cell with accepting No response receptor Response Nervous System Electrical signal Target cell Response Neuron Rapid, specific, short-lived Sites of hormone production all locations use hormones to regulate Hormones can be thebody produced by glands, specialized cells, or neurons iiiinto Hormones: Mechanisms of Action 1. Alter existing proteins peptidehormone e.g. change rates of enzymatic reactions [Enzyme] 2. Alter gene expression and protein synthesis e.g. Alter membrane permeability longterm effect Hormones: Classification Polypeptide Steroid takes longer Secretin pumped is Cortisol diffuse acrossmembraneintocell Not lipid soluble Lipid soluble Exocytosis Simple diffusion Pre-synthesized & stored in vesicles Synthesized on demand Dissolved in plasma Bound to transport proteins Short half-life Long half-life Receptors on cell membrane Receptors in cytoplasm or nucleus Activate 2nd Messenger systems Alter gene expression Modify existing proteins Induce protein synthesis Peptide Hormone Synthesis, Packaging, and Release 1 2 3 4 5 6 Messenger RNA on the Enzymes in the Secretory vesicles The secretory The hormone The prohormone ribosomes binds amino ER chop off the containing enzymes and vesicle releases moves into the passes from the acids into a peptide chain signal sequence, prohormone bud off the its contents by circulation for ER through the called a preprohormone creating an Golgi. The enzymes chop the exocytosis into transport to its Golgi complex. The chain is directed into inactive prohormone into one the extracellular target. the ER lumen by a signal prohormone. or more active peptides plus space. sequence of amino additional peptide fragments. acids. Endoplasmic reticulum (ER) Golgi complex To target Ribosome Active hormone Peptide Transport fragment vesicle 3 4 T 6 Secretory vesicle 5 Release signal Prohormone tailsmakethe mn hormone pronormone Capillary 2 inactive thisstepprevents endothelium thehormonereacting 1 withsomethingelse Signal Cytoplasm ECF Plasma sequence Preprohormone mRNA mm Figure 7-3, steps 1–6 Peptide Hormone: Action Activate membrane receptors and signal transduction Rapid cellular response Opens ion channel because hormones act Second messenger system on existing proteins phosphorylate KEY Proteins TK = Tyrosine kinase AE = Amplifier enzyme Cellular response G = G protein Figure 7-4 Steroid Synthesis generation of steriodhormone Petebindstoreceptor mrna nondetffffrotien modifies side chain for the steriod her a mitochondria cholesterol passbackthe free to modify release the sterloo Steroid Hormones: Action Blood Steroid Cell surface receptor 1 Most hydrophobic steroids are bound to vessel hormone plasma protein carriers. Only unbound hormones can diffuse into the target cell. 2a Rapid responses 1 2 Steroid hormone receptors are in the Protein 2 cytoplasm or nucleus. carrier Nucleus Cytoplasmic 2a Some steroid hormones also bind to Nuclear membrane receptors that use second receptor receptor messenger systems to create rapid cellular responses. DNA Interstitial 3 The receptor-hormone complex binds to fluid DNA and activates or represses one or 3 more genes. Endoplasmic reticulum Transcription Cell 4 Activated genes create new mRNA that produces mRNA membrane 5 moves back to the cytoplasm. 4 New proteins Translation 5 Translation produces new proteins for cell processes. Figure 7-5 Hormone Interactions 1. Permissiveness: one 2.Synergism: the combined effect 3. Antagonism: one hormone hormone enhances cellular of multiple hormones exceeds the decreases the cellular response response to another hormone sum of their individual effects to another hormone HE cancausethesameeffect in the s'tronger a together hormones A & B Cellular Response hormone B hormone A Time Hormone Regulation Sensor & Integrator Trophic hormones: endocrine regulation of hormonal release Often involves the hypothalamus-anterior pituitary axis Hypothalamus-anterior pituitary axis HYPOTHALAMUS 1 1 Neurons synthesizing trophic hormones release them into capillaries of the portal system. Capillary bed 2 Artery 2 Portal vessels carry the trophic hormones directly to the anterior pituitary. 3 Endocrine cells release POSTERIOR PITUITARY 3 their hormones into the second set of capillaries Capillary bed for distribution to the rest of the body. ANTERIOR PITUITARY Veins TO TARGET ORGANS Figure 7-16 Hypothalamus-anterior pituitary axis HYPOTHALAMUS Growth Hormone ACTH TSH LH FSH Prolactin IGF Cortisol Thyroxine Sex hormone secretion Gamete production Metabolic actions Breast growth Stress response Metabolic rate Milk production Growth Endocrine Pathologies Hypersecretion: excess hormone secretion Loss of feed back regulation excess hormone production Hyposecretion: deficient hormone secretion Loss/deficiency of hormone production Target cell pathologies Loss/down-regulation of target cell receptor Transduction of signal in target cells Review Negative feedback control loops allow us to regulate physiological function Local communication regulate the state of nearby cells Nervous system provides rapid but short lasting shifts in physiology, whereas the endocrine system produce slower but longer lasting affects The membrane permeability of peptide hormones and steroid hormones alters the nature and speed of their actions Endocrine responses can involve complicated cascades that can be regulated at various step Lectures 2 + 3 Finish hormonal control (end of lecture 2) Learn how ion concentration gradients and membrane permeability impact membrane potential Observe that changes in membrane permeability (Na+ & K+) cause the formation of action potentials Understand that action potentials are triggered by local current flow (a graded potential) Learn that the strength of graded potentials depends on resistance to current flow Observe that myelination increase the speed of AP Hormone Regulation Sensor & Integrator Trophic hormones: endocrine regulation of hormonal release Often involves the hypothalamus-anterior pituitary axis Hypothalamus-anterior pituitary axis HYPOTHALAMUS 1 1 Neurons synthesizing trophic hormones release them into capillaries of the portal system. Capillary bed 2 Artery 2 Portal vessels carry the trophic hormones directly to the anterior pituitary. 3 Endocrine cells release POSTERIOR PITUITARY 3 their hormones into the second set of capillaries Capillary bed for distribution to the rest of the body. ANTERIOR PITUITARY Veins TO TARGET ORGANS Figure 7-16 Hypothalamus-anterior pituitary axis HYPOTHALAMUS Growth Hormone ACTH TSH LH FSH liver Prolactin IGF Cortisol Thyroxine I Sex hormone secretion Gamete production Metabolic actions Breast growth Stress response Metabolic rate Milk production Growth non'm Endocrine Pathologies Hypersecretion: excess hormone secretion Loss of feed back regulation 14 It touch hormone excess hormone production Hyposecretion: deficient hormone secretion Loss/deficiency of hormone production Target cell pathologies Loss/down-regulation of target cell receptor signal not relieved not Transduction of signal in target cells enough hormone Review: homeostasis and communication in the body beable to explain each indetail Negative feedback control loops allow us to regulate physiological function Local communication regulate the state of nearby cells Nervous system provides rapid but short lasting shifts in physiology, whereas the endocrine system produce slower but longer lasting affects The membrane permeability of peptide hormones and steroid hormones alters the nature and speed of their actions Endocrine responses can involve complicated cascades that can be regulated at various steps E109 Lecture 3: Nervous System I Paul de Koninck Organization of the Nervous System bearrunning u fear signalissent to afferentneurons afferentneurons sendsignalto centralnervous system youcannot changethestrength ofan actionpotent but youcan changespeed Figure 8-1 Cells of the Nervous System Glial Cells Neurons dendrites Input signal Caffrey c neurons nucleus astrocytes cleansthehouse cell body Integration i deceives 59.9.1 signal enough in axon axon hillock ina m 1191119 besent oligodendrocytes incentralnervoussystem myelin sheath axon insulatingtheaxon Preventschargeloss Schwann cells inpns Output signal post-synaptic neuron stem cells Chemical Disequilibrium 160 140 KEY Na+ Ion concentration (mmol/L) 120 I K+ 100 Cl- 80 HCO3 - Proteins 60 40 20 Intracellular fluid Interstitial fluid Plasma howmanytransporters arethere aretheyopen there4open morepermeability Permeability: how readily a given substance (ion) moves across a membrane. Membrane Potential: Nernst Equation Cell Membrane Cytoplasm Extracellular fluid K+ K+ Na+ K+ K+ K+ K+ Na+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ K+ K+ + K+ K+ K K+K+ Na+ Na+ Na+ K+ Na+ Na+ K+ K+ Na+ Na+ Ek+ = 61 log (1/29) = -90 mV Charge permeability 1membrane potential Resting Membrane Potential: charge inside vs outside (-) Cell Membrane Dynamic changes in membrane permeability Cytoplasm Extracellular fluid to Na and K lead to action potentials + + Na+ Na+ K+ K+ K+ K+ K+ Na+ K+ Na+ K+ Na+ Na+ K+ K+ Na+ - 70 mV ENa +60 0 -70 Vm -90 EK changepermiabilityofthemembraneto potassiumleak channels always on which change membranepotential is the to  7 Resting Membrane Potential: charge inside vs outside (-) Cell Membrane At rest, we have some K+ permeability, but Cytoplasm Extracellular fluid nearly none for Na+. So, we sit at -70 mV. Na+ Na+ K+ K+ K+ K+ K+ Na+ K+ Na+ K+ Na+ Na+ K+ K+ Na+ - 70 mV ENa +60 0 -70 Vm -90 EK Phases of the action potential 1 Resting basic shape of 2 Rising (rapid depolarization) action potential 3 Overshoot (peak) 30 4 Falling (repolarization) 10 Membrane potential (mV) 3 5 Recovery (undershoot) 0 4 2 -30 Threshold -70 1 5 0 1 2 3 4 Time (ms) Resting Phase: driven by permeability of K+ inactivation Gothingcan gointo unless its charged a toldtoopen 30 0 -70 Rising Phase (depolarization): high permeability for Na+ mm in theopenconfiguratio 30 causing permeability to rise 0 -70 Falling Phase (repolarization): high permeability for K+ potassium gate is open while sodium ÑgE0ÑÑ 30 is inactivated 5 0 causing permeability -70 to drop Recovery Phase (undershoot): back to resting permeability Potassium gates are slow to close undershoo leading to 0 30 0 -70 Phases of the action potential 1 Resting: K+ permeability determines Vm 2 Rising: Voltage gated Na+ channels cause depolarization if 3 Overshoot: Na+ inactivation gates close, K+ channels open 4 Falling: K+ flows out of the cell (repolarization) 5 Recovery: K+ channels close and slowly restore Vm 30 3 10 Membrane potential (mV) 0 4 2 -30 Threshold -70 1 5 0 1 2 3 4 Time (ms) Changes in Permeability AP initiation through positive feedback ACTION POTENTIAL Rising phase Peak Falling phase Na+ enters timecontrols how cell. channels longthese are open To stop cycle, Na+ channel slower Na+ channel activation gates + Feedback cycle inactivation gate open rapidly. closes (see Fig. 8.10). More depolarization triggers Depolarization Slow K+ K+ leaves channels open. Repolarization cell. Action Potential Propagation Action Potential Propagation Refractory Periods Both Na+ Both channels channels Na+ channels close and Na+ channels reset to original position closed open channels K+ channels open while K+ channels remain open closed Na+ Na+ and K+ channels K+ K+ K+ Absolute refractory period Relative refractory period Membrane potential (mV) Action potential Ion permeability Na+ K+ High High Excitability sincethesodiumchannels Increasing are inactivated they partybetoldto Tibility Zero Time (msec) what thechance is that  e p n you Propagation Rates/Graded potentials The rate of action potential propagation depends on the resistance of the axon to current loss Increased resistance to current loss across the membrane Amplitude of graded maintains signal strength over potential (mV) longer distance Distance Distance Stimulus point of origin Propagation Rates Speed of action potential in neuron influenced by Diameter of axon Larger axons are faster Resistance of axon membrane to ion leakage out of the cell Myelinated axons are faster Schwann cells Saltatory Conduction Myelin Degeneration Myelin degeneration can result in significant loss of function Diseases: Multiple Sclerosis, Meylitis, Leukodystrophy Review Ion concentration gradients and membrane permeability determine membrane potential in cells Dynamic changes in membrane permeability (Na+ & K+) cause the development of an action potential Action potentials are triggered by local current flow (a graded potential) The strength of graded potentials depends on resistance to current flow Myelination increase the speed of AP propagation