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

The β1 subunit of voltage‐gated sodium channels, Na v β1, 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 Na v β1 subneuronal and regional expression. Na v β1 was enriched at axon initial segments (AIS) and nodes of Ranvier. Na v β1 expression at the AIS was detected throughout the brain, predominantly in the hippocampus, cortex, and cerebellum. Despite expression of Na v β1 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 Na v β1 coexpressed with Na v 1.1, Na v 1.2, and Na v 1.6 subunits. The disruption of Na v β1 AIS expression by a human epilepsy‐causing C121W genetic mutation in Na v β1 was also investigated using a mouse model. AIS expression of Na v β1 was reduced by approximately 50% in mice heterozygous for the C121W mutation and was abolished in homozygotes, suggesting that loss of Na v α subunit modulation by Na v β1 contributes to the mechanism of epileptogenesis in these animals as well as in patients. J. Comp. Neurol. 523:814–830, 2015. © 2015 Wiley Periodicals, Inc.