Trafficking mechanisms underlying neuronal voltage-gated ion channel localization at the axon initial segment.

Helene Vacher, James Trimmer

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Voltage-gated ion channels are diverse and fundamental determinants of neuronal intrinsic excitability. Voltage-gated K(+) (Kv) and Na(+) (Nav) channels play complex yet fundamentally important roles in determining intrinsic excitability. The Kv and Nav channels located at the axon initial segment (AIS) play a unique and especially important role in generating neuronal output in the form of anterograde axonal and backpropagating action potentials. Aberrant intrinsic excitability in individual neurons within networks contributes to synchronous neuronal activity leading to seizures. Mutations in ion channel genes give rise to a variety of seizure-related "channelopathies," and many of the ion channel subunits associated with epilepsy mutations are localized at the AIS, making this a hotspot for epileptogenesis. Here we review the cellular mechanisms that underlie the trafficking of Kv and Nav channels found at the AIS, and how Kv and Nav channel mutations associated with epilepsy can alter these processes. Wiley Periodicals, Inc.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalEpilepsia
Volume53 Suppl 9
StatePublished - Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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