J Comp Neurol. 2014 Nov 25. doi: 10.1002/cne.23715. [Epub ahead of print]
Wimmer, VC; Harty, RC; Richards, KL; Phillips, AM; Miyazaki, H; Nukina, N; Petrou, S
Florey Institute of Neuroscience and Mental Health, Cnr Genetics Lane and Royal Parade, Victoria, 3010, Australia.
The β1 subunit of voltage-gated sodium channels, Nav 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 Nav β1 sub-neuronal and regional expression. Nav β1 was enriched at axon initial segments (AIS) and nodes of Ranvier. Nav β1 expression at the AIS was detected throughout the brain, predominantly in the hippocampus, cortex and cerebellum. Despite expression of Nav β1 in both excitatory and inhibitory AIS's 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 Nav β1 co-expressed with Nav 1.1, Nav 1.2 and Nav 1.6 subunits. The disruption of Nav β1 AIS expression by a human epilepsy-causing C121W genetic mutation in Nav β1 was also investigated using a mouse model. AIS expression of Nav β1 was reduced by approximately 50% in mice heterozygous for the C121W mutation and abolished in homozygotes, suggesting that loss of Nav α subunit modulation by Nav β1 contributes to the mechanism of epileptogenesis in these animals as well as patients.
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