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USC BISC 307L - Synaptic Transmission
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Action PotentialsIonic Basis for Action PotentialsNa+ influxdepolarizationopening Na+ channelsboth concentration gradient and electrical gradient are inward for Na+ and Ca2+This is how we are used to seeing it. This describes what the Action potential is doing in one little patch of membrane at multiple timesVoltage vs. timeAction Potential ConductionHow the action potential functions ALONG the axon not as a function of time.Voltage vs. distance along the axonMiddle is the action potentialNa+ current coming into the cell through Na+ ion channelsCircuit to the right is the current flowing down the axon and some moves out through the resistance and capacitance of the membrane (through the leaky ion channels)This is a frozen moment of time- whole axon at one timeAs it flows out of the cell across the membrane capacitance, it DEPOLARIZES until it depolarizes to thresholdThere are voltage gated Na+ channels to the right and when the membrane is depolarized enough, the Na+ channels flip open allowing Na+ to rush in. At first it's just a trickle and this Na+ moves right back out the leaky K+ channels- repolarizing the membrane. But this isn’t all that happens because the outward current flow is still happening and as more of this flows out, there is more and more depolarization. When you get to the point where so many Na+ is flowing inward that it exceeds the amount flowing outward that is threshold. Current is coming in faster than the open channels can carry it out again = net inward current, explosive positive feedback cycleWhen this happens the action potential is moving to the rightThis happens continuously in a wave, depolarizing the membrane ahead of it as it goes. RegenerativeWhat’s happening behind the action potential? Na+ coming in is flowing to the left but there are more open channels than normal. There are additional K+ channels open than ahead of the action potential. The K+ permeability increases more slowly with depolarization and they close more slowly.K+ is flowing out through open channels right behind the action potentialA lot of current flowing behind the membrane flows out again, and REPOLARIZES the membraneThis extra flowing of K+ makes the membrane more negative inside explaining the falling phase in the action potentialWay off to the left, it's been so long that everything is back at restNa+ inactivation= depolarization opens Na+ channels and then closes them, opening happens immediately and the closing takes a while. Inactivation gate. Right after the peak of the action potential, not only are there open K+ channels but the Na+ channels are inactivatedThe time right behind the action potential is the refractory period making the membrane unexcitable for a little whileWhen the action potential gets to the end of the axon it stopsIt can never fire any faster than the refractory period dictatesIf you were to plot the membrane potential as a function of distance: you would get the line that is below the figurebig axons conduct faster- see this a lot in invertebrates with their escape mechanisms are very fastvertebrates don’t need large axons because they have developed myelin sheathMyelinated Axons: Saltatory ConductionSegments of myelin- glial cell that wraps around the axon. Not just membrane (living process of the cell)This has two electrical consequences1. Increases resistance of the wall of the axon- so current tends to not leak out through the membrane and continues down2. Reduces the capacitance of the wall of the axon- low ability to store charge and therefore this minimizes the leakage alsoSo the current basically flows from node to node without leaking. They leak only at the node so current coming in at one node is focused on depolarizing the next node further downModifications1. In the nodal membrane of the axon there are a lot of voltage gated Na+ channels at extremely high density and no K+ channel. K+ channels are on either side of the node. So this concentrates Na+ to depolarize the next node. Saltatory conduction = jumping conductionresult in so much current that it is usually enough to depolarize the third node downcan achieve up to 100 meters/second or 150 meters/secondChannelopathies (most rare)Na+ ChannelsHyperkalemic periodic paralysisIncomplete inactivation of Na+ channelMeans it would stay depolarized for too longHappens once in a while, triggered by high K+ levels in the bloodForms of epilepsyCa2+ channelsLambert-Eaton myasthenic syndromeAutoimmune destruction of presynaptic Ca2+ channels at neuromuscular junctionsMuscle weaknessHypokalemic periodic paralysisTriggered by low external Ca2+ concentrationDue to a mutated Ca2+ channel in the T-Tubule membrane or**Hypokalemic = low plasma potassium concentration. Resulting affect on the repolarization of the action potentialmalignant hyperthermiaabnormal ryanodine receptor (Ca2+ release channel is SR)abnormal Ca2+ channel in sarcoplasmic reticular membranewhen this happens, stays open too long letting out too much Ca2+ triggering muscle contractions and heat released by these contractions trigger hypothermiahave no symptoms except with gaseous anestheticsK+ ChannelsLong Q-T syndrome (most types)Prolonged action potential in heartCl- ChannelsMyotonia congenitalDelays relaxation of skeletal muscleCl- channels defective and so repolarization cannot happen as fastCystic fibrosisDefective CFTR (Cl- channel)Synaptic TransmissionGap JunctionsElectrical synapseHow does the action potential get transmitted?Simplest synapseSignal going in the downward directionUpstream = presynaptic side and downstream = postsynaptic sideConnexins form hexameric structure and assemble into a connexon which has a large aqueous pore that can pass all ions (current)Current flows into the axon terminal and then right into the postsynaptic cell and then flows out across the postsynaptic membrane depolarizing the postsynaptic membrane and thus the action potential is transmittedFast, reliable but not as modifiableUsed in a lot of places (cardiac muscle cells)Makes the action potential travel in a wave in the heartGap junctions (green) between cardiac cellsBISC 307L 1st Edition Lecture 6Current Lecture Action Potentials- Ionic Basis for Action Potentialso Na+ influxdepolarizationopening Na+ channelso both concentration gradient and electrical gradient are inward for Na+ and Ca2+o This is how we are used to seeing it. This describes what the Action potential is doing in one little patch of membrane at


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