PT  - JOURNAL ARTICLE
AU  - Mara Almog
AU  - Tal Barkai
AU  - Angelika Lampert
AU  - Alon Korngreen
TI  - Voltage-gated sodium channels in neocortical pyramidal neurons display Cole-Moore activation kinetics
AID  - 10.1101/164210
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 164210
4099  - http://biorxiv.org/content/early/2017/07/16/164210.short
4100  - http://biorxiv.org/content/early/2017/07/16/164210.full
AB  - Exploring the properties of action potentials is a crucial step towards 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. Most models of voltage-gated sodium channels assume it obeys a concerted Hodgkin and Huxley kinetic gating scheme. 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. This may have key implications for the role of sodium channels in synaptic integration and action potential generation.