BISC 307L 1st Edition Lecture 6 Current Lecture Action Potentials Ionic Basis for Action Potentials o Na influx depolarization opening Na channels o 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 multiple times o Voltage vs time o Action Potential Conduction o How the action potential functions ALONG the axon not as a function of time o Voltage vs distance along the axon o Middle is the action potential o Na current coming into the cell through Na ion channels o Circuit 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 o This is a frozen moment of time whole axon at one time o As it flows out of the cell across the membrane capacitance it DEPOLARIZES until it depolarizes to threshold o There 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 channelsrepolarizing 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 cycle o When this happens the action potential is moving to the right o This happens continuously in a wave depolarizing the membrane ahead of it as it goes Regenerative o What 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 o K is flowing out through open channels right behind the action potential o A lot of current flowing behind the membrane flows out again and REPOLARIZES the membrane o This extra flowing of K makes the membrane more negative inside explaining the falling phase in the action potential o Way off to the left it s been so long that everything is back at rest o Na 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 inactivated o The time right behind the action potential is the refractory period making the membrane unexcitable for a little while o When the action potential gets to the end of the axon it stops o It can never fire any faster than the refractory period dictates o If you were to plot the membrane potential as a function of distance you would get the line that is below the figure o big axons conduct faster see this a lot in invertebrates with their escape mechanisms are very fast o vertebrates don t need large axons because they have developed myelin sheath Myelinated Axons Saltatory Conduction o Segments of myelin glial cell that wraps around the axon Not just membrane living process of the cell o This has two electrical consequences 1 Increases resistance of the wall of the axon so current tends to not leak out through the membrane and continues down 2 Reduces the capacitance of the wall of the axon low ability to store charge and therefore this minimizes the leakage also o So 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 down o Modifications 1 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 conduction o result in so much current that it is usually enough to depolarize the third node down o can achieve up to 100 meters second or 150 meters second Channelopathies most rare o Na Channels Hyperkalemic periodic paralysis Incomplete inactivation of Na channel Means it would stay depolarized for too long Happens once in a while triggered by high K levels in the blood Forms of epilepsy o Ca2 channels Lambert Eaton myasthenic syndrome Autoimmune destruction of presynaptic Ca2 channels at neuromuscular junctions Muscle weakness Hypokalemic periodic paralysis Triggered by low external Ca2 concentration Due to a mutated Ca2 channel in the T Tubule membrane or Hypokalemic low plasma potassium concentration Resulting affect on the repolarization of the action potential malignant hyperthermia abnormal ryanodine receptor Ca2 release channel is SR abnormal Ca2 channel in sarcoplasmic reticular membrane when this happens stays open too long letting out too much Ca2 triggering muscle contractions and heat released by these contractions trigger hypothermia have no symptoms except with gaseous anesthetics o K Channels Long Q T syndrome most types Prolonged action potential in heart o Cl Channels Myotonia congenital Delays relaxation of skeletal muscle Cl channels defective and so repolarization cannot happen as fast Cystic fibrosis Defective CFTR Cl channel Synaptic Transmission Gap Junctions o Electrical synapse o How does the action potential get transmitted o Simplest synapse o Signal going in the downward direction o Upstream presynaptic side and downstream postsynaptic side o Connexins form hexameric structure and assemble into a connexon which has a large aqueous pore that can pass all ions current o 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 transmitted o Fast reliable but not as modifiable o Used in a lot of places cardiac muscle cells Makes the action potential travel in a wave in the heart cardiac cells Gap junctions green between