Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons

Michel Royeck, Marie Therese Horstmann, Stefan Remy, Margit Reitze, Yoel Yaari, Heinz Beck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

In many neuron types, the axon initial segment (AIS) has the lowest threshold for action potential generation. Its active properties are determined by the targeted expression of specific voltage-gated channel subunits. We show that the Na+ channel NaV1.6 displays a striking aggregation at the AIS of cortical neurons. To assess the functional role of this subunit, we used Scn8amed mice that are deficient for Na V1.6 subunits but still display prominent Na+ channel aggregation at the AIS. In CA1 pyramidal cells from Scn8amed mice, we found a depolarizing shift in the voltage dependence of activation of the transient Na+ current (INaT), indicating that Na V1.6 subunits activate at more negative voltages than other Na V subunits. Additionally, persistent and resurgent Na+ currents were significantly reduced. Current-clamp recordings revealed a significant elevation of spike threshold in Scn8amed mice as well as a shortening of the estimated delay between spike initiation at the AIS and its arrival at the soma. In combination with simulations using a realistic computer model of a CA1 pyramidal cell, our results imply that a hyperpolarized voltage dependence of activation of AIS NaV1.6 channels is important both in determining spike threshold and localizing spike initiation to the AIS. In addition to altered spike initiation, Scn8amed mice also showed a strongly reduced spike gain as expected with combined changes in persistent and resurgent currents and spike threshold. These results suggest that Na V1.6 subunits at the AIS contribute significantly to its role as spike trigger zone and shape repetitive discharge properties of CA1 neurons.

Original languageEnglish
Pages (from-to)2361-2380
Number of pages20
JournalJournal of Neurophysiology
Volume100
Issue number4
DOIs
StatePublished - Oct 2008

Fingerprint

Dive into the research topics of 'Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons'. Together they form a unique fingerprint.

Cite this