Voltage-Gated Sodium Channels in Neocortical Pyramidal Neurons Display Cole-Moore Activation Kinetics

Frontiers in Cellular Neuroscience
Mara AlmogAlon Korngreen

Abstract

Exploring the properties of action potentials is a crucial step toward a better understanding of the computational properties of single neurons and neural networks. The voltage-gated sodium channel is a key player in action potential generation. A comprehensive grasp of the gating mechanism of this channel can shed light on the biophysics of action potential generation. However, most models of voltage-gated sodium channels assume a concerted Hodgkin and Huxley kinetic gating scheme. However, it is not clear if Hodgkin and Huxley models are suitable for use in action potential simulations of central nervous system neurons. To resolve this, we investigated the activation kinetics of voltage-gated sodium channels. Here we performed high resolution voltage-clamp experiments from nucleated patches extracted from the soma of layer 5 (L5) cortical pyramidal neurons in rat brain slices. We show that the gating mechanism does not follow traditional Hodgkin and Huxley kinetics and that much of the channel voltage-dependence is probably due to rapid closed-closed transitions that lead to substantial onset latency reminiscent of the Cole-Moore effect observed in voltage-gated potassium conductances. Thus, the classical Hodgkin and Huxley d...Continue Reading

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Citations

May 8, 2021·Frontiers in Physiology·Andrew S Johnson, William Winlow
Nov 21, 2021·Nature Communications·Benjamin M ZemelHenrique von Gersdorff

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