Simulations%20of%20APs

Simulations%20of%20APs - IPHY 4720 Neurophysiology Computer...

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IPHY 4720 Neurophysiology Computer Simulations of the Action Potential **In addition to this handout, read pp. 186 – 188 in Enoka.** Background : Our understanding of how the action potential is generated is based on a series of voltage-clamp experiments on the squid giant axon carried out by Alan Hodgkin, Andrew Huxley, and Bernard Katz in the late 1940s and early 1950s. These experiments demonstrated that the action potential depends on three types of conductances: a K + conductance, a Na + conductance, and a nonselective leak conductance. These conductances involve three distinct types of ion channels: K + channels, Na + channels, and leakage channels that are permeable to K + , Na + and Cl . The membrane of the axon contains voltage-gated Na + channels, voltage-gated K + channels, and non-gated leak channels that are largely permeable to Cl ions. In response to a depolarizing current, the voltage-gated Na + channels start to open by a process termed activation. The increase in Na + conductance enables the positively charged Na + ions to enter the neuron. The influx of positive charge further depolarizes the membrane. At the same time, the depolarizing stimulus increases the outward flow of current through the K + and leak channels. The efflux of positive charge repolarizes the membrane back towards its resting potential. With small (subthreshold) depolarizations, the amount of outward current is greater than the amount of inward current due to the low membrane permeability to Na + . The net effect of the current, therefore, is to repolarize the membrane. Depolarization to the voltage threshold opens up just enough Na + channels so that the amount of positively charged Na + entering the axon is equal to the amount of positive charge leaving the axon through the K + and leak channels. When the membrane is depolarized slightly above the threshold, a few more Na + channels will open that increases Na + conductance even further and allows an even greater inward Na + current, and a greater depolarization. This regenerative depolarization opens up a large number of Na + channels so that the Na + conductance is much greater than the K + or leak conductance. As a result, the membrane potential approaches the Na + equilibrium potential ( E Na = +55 mV). The membrane does not remain depolarized for long for two reasons: 1. The Na + channels close due to a time-dependant process termed inactivation. 2. Voltage-gated K + channels are activated in response to depolarization. As the voltage-gated K + channels open, the extra efflux of K + ions changes the membrane potential to more negative values, so that V m approaches E K . Thus, voltage-gated Na + channels are controlled by two types of gates: an activation gate that opens upon depolarization and an inactivation gate that closes more slowly upon depolarization. Voltage-gated K + channels only possess an activation gate. Upon repolarization of the membrane after an action potential, the Na
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Simulations%20of%20APs - IPHY 4720 Neurophysiology Computer...

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