Channelpedia

PubMed 20133873


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1.6



Title: Functional reciprocity between Na+ channel Nav1.6 and beta1 subunits in the coordinated regulation of excitability and neurite outgrowth.

Authors: William J Brackenbury, Jeffrey D Calhoun, Chunling Chen, Haruko Miyazaki, Nobuyuki Nukina, Fumitaka Oyama, Barbara Ranscht, Lori L Isom

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2010 Feb 2 , 107, 2283-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20133873


Abstract
Voltage-gated Na(+) channel (VGSC) beta1 subunits regulate cell-cell adhesion and channel activity in vitro. We previously showed that beta1 promotes neurite outgrowth in cerebellar granule neurons (CGNs) via homophilic cell adhesion, fyn kinase, and contactin. Here we demonstrate that beta1-mediated neurite outgrowth requires Na(+) current (I(Na)) mediated by Na(v)1.6. In addition, beta1 is required for high-frequency action potential firing. Transient I(Na) is unchanged in Scn1b (beta1) null CGNs; however, the resurgent I(Na), thought to underlie high-frequency firing in Na(v)1.6-expressing cerebellar neurons, is reduced. The proportion of axon initial segments (AIS) expressing Na(v)1.6 is reduced in Scn1b null cerebellar neurons. In place of Na(v)1.6 at the AIS, we observed an increase in Na(v)1.1, whereas Na(v)1.2 was unchanged. This indicates that beta1 is required for normal localization of Na(v)1.6 at the AIS during the postnatal developmental switch to Na(v)1.6-mediated high-frequency firing. In agreement with this, beta1 is normally expressed with alpha subunits at the AIS of P14 CGNs. We propose reciprocity of function between beta1 and Na(v)1.6 such that beta1-mediated neurite outgrowth requires Na(v)1.6-mediated I(Na), and Na(v)1.6 localization and consequent high-frequency firing require beta1. We conclude that VGSC subunits function in macromolecular signaling complexes regulating both neuronal excitability and migration during cerebellar development.