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Sodium channel β1 subunit localizes to axon initial segments of excitatory and inhibitory neurons and shows regional heterogeneity in mouse brain
Author(s) -
Wimmer Verena C.,
Harty Rosemary C.,
Richards Kay L.,
Phillips A. Marie,
Miyazaki Haruko,
Nukiobuyuki,
Petrou Steven
Publication year - 2015
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23715
Subject(s) - sodium channel , inhibitory postsynaptic potential , excitatory postsynaptic potential , protein subunit , biology , axon , cerebellum , neuroscience , epileptogenesis , electrophysiology , hippocampus , microbiology and biotechnology , sodium , chemistry , biochemistry , gene , organic chemistry
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.