Action Potential: Fall 2024 Lecture Notes PDF

Summary

These notes cover action potentials in detail. The document explains the processes of depolarization, repolarization, and hyperpolarization. They are accompanied by diagrams, explaining how these electrical impulses occur and propagate, along with considerations of myelination.

Full Transcript

The Action Potential Chapter 4 – Discuss the key characteristics of action potentials – Learn about the generation of action potentials Learning from various sources objectives – Understand all of the steps of the action potential in...

The Action Potential Chapter 4 – Discuss the key characteristics of action potentials – Learn about the generation of action potentials Learning from various sources objectives – Understand all of the steps of the action potential in detail – Discuss how action potentials are conducted/propagated – Membrane potential changes when: – Concentrations of ions across membrane change – Membrane permeability to ions changes Changing the – Changes produce two types of signals – Graded potentials membrane – Incoming signals operating over short distances potential – Action potentials – Long-distance signals of axons – Changes in membrane potential are used as signals to receive, integrate, and send information – Convey information over long distances – Reversal of charge relative to extracellular space – Neural code based on frequency and pattern of action potentials – Action potential also called: – Spike – Nerve impulse – Discharge Key – Occur only in muscle and neuronal cells characteristics of action potentials From Dr. Zhou’s 2022 paper: https://www.mdpi.com/2073-4409/11/23/3889# – Terms describing membrane potential changes relative to resting membrane potential – Depolarization: decrease in membrane potential (moves toward zero and above) – Inside of membrane becomes less negative than resting membrane potential – Probability of producing impulse increases – Hyperpolarization: increase in membrane potential (away from zero) – Inside of membrane becomes more negative than resting membrane potential Changing the – Probability of producing impulse decreases membrane potential – The ups and downs of an action potential are very consistent – Oscilloscopes (voltage readers) often used to study action potentials – Four phases: – Resting & rising phase (depolarization) – Overshoot phase (depolarization) – Falling phase (repolarization) – Undershoot phase (hyperpolarization) Properties of action potentials – The generation of an action potential – Caused by depolarization of membrane beyond threshold from ANY source (whether “natural” or artificial) – “All-or-none” – Chain reaction – Example: foot puncture, stretch membrane of nerve fibers – Opens Na+-permeable channelsà Na+ influxà depolarized membraneà reaches thresholdà action potential Generating – The stimulation of multiple action potentials – Artificially inject current into a neuron with microelectrode action potentials – The generation of multiple action potentials – Firing frequency reflects the magnitude of the depolarizing current. – Therefore, the pattern of action potentials reflects how often neurons are being depolarized by magnitudes of varying strengths Generating action potentials – Optogenetics – we hijack membrane channel proteins to force depolarization or hyperpolarization with light – Introduction of foreign genes – Express membrane ion channels—open in response to light – In mouse brain, neurons firing controlled by light delivered by optic fiber Generating action potentials – Resting membrane potential of a resting neuron is approximately −70 mV – The cytoplasmic side of membrane is negatively charged relative to the Before we outside dive into the – The actual voltage difference varies from −40 mV to −90 mV action – Potential generated by: potential – Differences in ionic composition of ICF and ECF – Differences in plasma membrane permeability steps: recall the resting membrane potential – The steps/stages, in order by name & visuals – Be able to draw action potentials to scale – All the key numbers: – X axis – time in ms; duration What to know – Y axis – voltage in mV; magnitude about action – Resting potential, peak, hyperpolarization values potentials – What channels are involved at each step and how they are causing each step – I.e. what ions are they letting in or out? How does the movement of those ions cause changes in membrane potential? – Refractory periods: can not start anymore action potentials 1. Resting state: All gated Na+ and K+ channels are closed – Only leakage channels for Na+ and K+ are open Four steps of – Maintains the resting membrane potential the action – Each Na+ channel has two voltage- sensitive gates potential – – Activation gates: closed at rest; open with depolarization, allowing Step 1: Na+ to enter cell – Inactivation gates: open at rest; Resting state block channel once it is open to prevent more Na+ from entering cell – Each K+ channel has one voltage- sensitive gate – Closed at rest – Opens slowly with depolarization – The main sodium channels that contribute to our action potentials are voltage gated, with that voltage being -55mV Quick detour – Voltage-gated sodium channels are totally selective to sodium – The activation & inactivation gates provide a dual mechanism for about voltage channel closure gated channels because they play a major role – Functional properties of sodium channels – Open with little delay – Stay open for about 1 msec – Cannot be opened again immediately by depolarization – Absolute refractory period: channels are inactivated Quick detour – They are so crucial to every action potential that dysfunction causes about voltage major dysfunction or even fatality – In genetic disease – channelopathies gated – Example: generalized epilepsy with febrile seizures channels – Toxins as experimental tools because they – Puffer fish tetrodotoxin (TTX) - clogs Na+-permeable pore: block sodium channels play a major – Red tide (algae) saxitoxin—Na+ channel-blocking toxin role – Variety of toxins affect channels – Batrachotoxin (frog) blocks inactivation so channels remain open. – Similar effects from veratridine (lilies) and aconitine (buttercups) Quick detour – Differential toxin binding sites: clues about 3D structure of sodium about voltage channels gated channels because they play a major role – Voltage-gated potassium channels are gated to open at +30mV: – Potassium vs. sodium gates – Both open in response to depolarization. Quick detour – Potassium gates open later than sodium gates. about voltage – Delayed rectifier – Potassium conductance serves to rectify or reset membrane potential. gated – Structure: Four separate polypeptide subunits join to form a pore. channels because they play a major role 1. Resting state: All gated Na+ and K+ channels are closed – Only leakage channels for Na+ and K+ are open Four steps of – Maintains the resting membrane potential the action – Each Na+ channel has two voltage- sensitive gates potential – – Activation gates: closed at rest; open with depolarization, allowing Step 1: Na+ to enter cell – Inactivation gates: open at rest; Resting state block channel once it is open to prevent more Na+ from entering cell – Each K+ channel has one voltage- sensitive gate – Closed at rest – Opens slowly with depolarization 2. Depolarization: Na+ channels open – Depolarizing local currents open voltage-gated Na+ channels, and Na+ rushes into cell Four steps of – Na+ activation and inactivation gates open the action – Na+ influx causes more depolarization, which opens more potential – Na+ channels – As a result, ICF becomes less Step 2: negative Depolarization – At threshold (–55 to –50 mV), positive feedback causes opening of all Na+ channels – Results in large action potential spike – Membrane polarity jumps to +30 mV 3. Repolarization: Na+ channels are inactivating, and K+ channels open Four steps of – Na+ channel inactivation gates close the action – Membrane permeability to Na+ declines to resting state potential – – AP spike stops rising Step 3: – Voltage-gated K+ channels open Repolarization – K+ exits cell down its electrochemical gradient – Repolarization: membrane returns to resting membrane potential 4. Hyperpolarization: Some K+ channels remain open, and Na+ channels reset Four steps of the – Some K+ channels remain open, action potential – allowing excessive K+ efflux – Inside of membrane becomes more Step 4: negative than in resting state Hyperpolarization – This causes hyperpolarization of the membrane (slight dip below resting voltage) – Na+ channels also begin to reset Four steps of the action potential Four steps of the action potential – Not all depolarization events produce APs – For an axon to “fire,” depolarization must reach threshold voltage to The action trigger AP potential – At threshold: – Membrane is depolarized by 15 to 20 mV threshold is – Na+ permeability increases all-or-none – – Na+ influx exceeds K+ efflux The positive feedback cycle begins – All-or-None: An AP either happens completely, or does not happen at all – Propagation allows AP to be transmitted from origin down entire axon length toward terminals Action – Na+ influx through voltage gates in one potential membrane area cause local currents that cause opening of Na+ voltage propagation gates in adjacent membrane areas – Leads to depolarization of that area, which in turn causes depolarization in next area – Once initiated, an AP is self- propagating – In nonmyelinated axons, each successive segment of membrane Action depolarizes, then repolarizes potential – Propagation in myelinated axons differs propagation – Since Na+ channels closer to the AP origin are still inactivated, no new AP is generated there – AP occurs only in a forward direction Action potential propagation – All action potentials are alike and are independent of stimulus intensity Stimulus – CNS tells difference between a weak stimulus and a strong one strength & AP by frequency of impulses generation – Frequency is number of impulses (APs) received per second – Higher frequencies mean stronger stimulus – Refractory period: time in which neuron cannot trigger another AP – Voltage-gated Na+ channels are open, so neuron cannot respond to another stimulus Refractory – Two types – Absolute refractory period periods – Time from opening of Na+ channels until resetting of the channels – Ensures that each AP is an all-or-none event – Enforces one-way transmission of nerve impulses – Relative refractory period – Follows absolute refractory period – Most Na+ channels have returned to their resting state – Some K+ channels still open – Repolarization is occurring – Threshold for AP generation is Refractory elevated – Only exceptionally strong periods stimulus could stimulate an AP – Think of a disobedient (refractory) dog – if he is absolutely refractory he will never come when called, but if he is relatively refractory, he may come but only if you call loud enough – APs occur only in axons, not other cell areas – AP conduction velocities in axons vary widely – Rate of AP propagation depends on two factors: 1. Axon diameter – Larger-diameter fibers have less resistance to local current flow, so have faster impulse conduction Action 2. Degree of myelination potential – Two types of conduction depending on presence or absence of myelin – Continuous conduction conduction – Saltatory conduction velocity – Continuous conduction: slow conduction that occurs in nonmyelinated axons Action potential propagation – Saltatory conduction: occurs only in myelinated axons and is about 30 times faster – Myelin sheaths insulate and prevent leakage of charge – Voltage-gated Na+ channels are located at myelin sheath gaps – APs generated only at gaps Action – Electrical signal appears to jump rapidly from gap to gap potential propagation – Multiple sclerosis (MS) is an autoimmune disease that affects primarily young adults – Myelin sheaths in CNS are destroyed when immune system attacks myelin – Turns myelin into hardened lesions called scleroses – Impulse conduction slows and eventually ceases – Demyelinated axons increase Na+ channels, causing cycles of relapse and remission Clinical connection – myelin sheath disorders Quiz hint! – Key voltage numbers related to action potentials – Extended labor day holiday! Don’t come to class next Tuesday! Reminder: no – (I teach Mon-Wed classes and it completely desynchronizes all of class next my sections if I don’t also give the Tues-Thurs peeps the day off) – Check your other classes though, they may still be on for Tues Tuesday – Enjoy the long weekend! Questions?

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