The sodium channel accessory subunit Navβ1 regulates neuronal excitability through modulation of repolarizing Voltage-gated K+ channels

Céline Marionneau, Yarimar Carrasquillo, Aaron J. Norris, R. Reid Townsend, Lori L. Isom, Andrew J. Link, Jeanne M. Nerbonne

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The channel pore-forming α subunit Kv4.2 is a major constituent of A-type (IA) potassium currents and a key regulator of neuronal membraneexcitability. Multiple mechanisms regulate the properties, subcellular targeting, and cell-surface expression of Kv4.2-encoded channels. In the present study, shotgun proteomic analyses of immunoprecipitated mouse brain Kv4.2 channel complexes unexpectedly identified the voltage-gated Na+ channel accessory subunit Navβ1. Voltage-clamp and current-clamp recordings revealed that knockdown of Navβ1 decreases IA densities in isolated cortical neurons and that action potential waveforms are prolonged and repetitive firing is increased in Scn1b-null cortical pyramidal neurons lacking Navβ1. Biochemical and voltage-clamp experiments further demonstrated that Navβ1 interacts with and increases the stability of the heterologously expressed Kv4.2 protein, resulting in greater total and cell-surface Kv4.2 protein expression and in larger Kv4.2-encoded current densities. Together, the results presented here identify Navβ1 as a component of native neuronal Kv4.2-encoded IA channel complexes and a novel regulator of IA channel densities and neuronal excitability.

Original languageEnglish
Pages (from-to)5716-5727
Number of pages12
JournalJournal of Neuroscience
Volume32
Issue number17
DOIs
StatePublished - Apr 25 2012

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