Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4348029 | Neuroscience Letters | 2008 | 5 Pages |
The voltage-gated sodium channel α subunit Nav1.6, encoded by the Scn8a gene, accumulates at high density at mature nodes of Ranvier of myelinated axons, replacing the Nav1.2 channels found at nodes earlier in development. To investigate this preferential expression of Nav1.6 at adult nodes, we examined isoform-specific expression of sodium channels in mice heterozygous for a null mutation in Scn8a. Immunoblots from these +/− mice had 50% of the wild-type level of Nav1.6 protein, and their optic-nerve nodes of Ranvier had correspondingly less anti-Nav1.6 immunofluorescence. Protein level and nodal immunofluorescence of the Nav1.2 α subunit increased in Scn8a+/− mice, keeping total sodium channel expression approximately constant despite partial loss of Nav1.6 channels. The results are consistent with a model in which Nav1.6 and Nav1.2 compete for binding partners at sites of high channel density, such as nodes of Ranvier. We suggest that Nav1.6 channels normally occupy most of the molecular machinery responsible for channel clustering because they have higher binding affinity, and not because they are exclusively recognized by mechanisms for transport and insertion of sodium channels in myelinated axons. The reduced amount of Nav1.6 protein in Scn8a+/− mice is apparently insufficient to saturate the nodal binding sites, allowing Nav1.2 channels to compete more successfully.