Nav1.6 but not KCa3.1 channels contribute to heterogeneity in coding abilities and dynamics of action potentials in the L5 neocortical pyramidal neurons

Electrophysiological and genetic studies reveal two major subclasses of layer 5 (L5) neocortical pyramidal neurons that differ in electrical parameters and afterhyperpolarization. KCa3.1 channels are identified as contributors to slow afterhyperpolarization (sAHP), and they are expressed by one subclass of L5 neurons. Yet, the impact of class-specific sAHP and KCa3.1 channels on coding abilities of the L5 neurons and dynamics of their action potentials (APs) remains poorly understood. Here, by comparing sAHP+ neurons to those with weak sAHP we investigate differences between the two groups in coding and AP features to address the question of whether those differences are due to contribution of KCa3.1 or other channels. Using patch clamp electrophysiology, channel blockers, and immunohistochemistry we demonstrate that Nav1.6 channels but not KCa3.1 channels affect the threshold of AP, its dynamics and coding abilities of the L5 cells. Immunohistochemical data show that KCa3.1+ and KCa3.1- neurons share the same pattern of Nav1.6 expression in the soma and axonal initial segment, thus they may differ in quantity of the channels expressed. Our study links the Nav1.6 function underlying regulation of voltage threshold to the abilities of L5 neurons to encode high frequencies. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

Electrophysiological and genetic studies have identified two major subclasses of L5 neocortical pyramidal neurons, with one subclass expressing KCa3.1 channels and the other exhibiting weak afterhyperpolarization. This study demonstrates that Nav1.6 channels, rather than KCa3.1 channels, have an impact on the threshold, dynamics, and coding abilities of these neurons. The findings suggest a link between Nav1.6 function and the ability of L5 neurons to encode high frequencies.