Sodium channel β1 subunit localizes to axon initial segments of excitatory and inhibitory neurons and shows regional heterogeneity in mouse brain

Verena C. Wimmer, Rosemary C. Harty, Kay L. Richards, A. Marie Phillips, Haruko Miyazaki, Nobuyuki Nukina, Steven Petrou

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The β1 subunit of voltage-gated sodium channels, Navβ1, plays multiple roles in neurons spanning electrophysiological modulation of sodium channel α subunits to cell adhesion and neurite outgrowth. This study used immunohistochemistry to investigate Navβ1 subneuronal and regional expression. Navβ1 was enriched at axon initial segments (AIS) and nodes of Ranvier. Navβ1 expression at the AIS was detected throughout the brain, predominantly in the hippocampus, cortex, and cerebellum. Despite expression of Navβ1 in both excitatory and inhibitory AIS, it displayed a marked and fine-grained heterogeneity of expression. Such heterogeneity could have important implications for the tuning of single neuronal and regional excitability, especially in view of the fact that Navβ1 coexpressed with Nav1.1, Nav1.2, and Nav1.6 subunits. The disruption of Navβ1 AIS expression by a human epilepsy-causing C121W genetic mutation in Navβ1 was also investigated using a mouse model. AIS expression of Navβ1 was reduced by approximately 50% in mice heterozygous for the C121W mutation and was abolished in homozygotes, suggesting that loss of Navα subunit modulation by Navβ1 contributes to the mechanism of epileptogenesis in these animals as well as in patients.

Original languageEnglish
Pages (from-to)814-830
Number of pages17
JournalJournal of Comparative Neurology
Volume523
Issue number5
DOIs
Publication statusPublished - Apr 1 2015
Externally publishedYes

Keywords

  • AB_10673030
  • AB_177621
  • AB_2184030
  • AB_2184197
  • AB_2238842
  • Axon initial segment
  • C121W
  • Epilepsy
  • Naβ1
  • Nif-0000-00262
  • Rid_000081
  • SciRes_000137
  • SCN1B
  • Voltage-gated sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)

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