04-ActionPotential-Fall2024.pdf

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?