Mice Lacking Sodium Channel beta 1 Subunits Display Defects in Neuronal Excitability, Sodium Channel Expression, and Nodal Architecture

Sodium channel beta 1 subunits modulate alpha subunit gating and cell surface expression and participate in cell adhesive interactions in vitro. beta 1(-/-) mice appear ataxic and display spontaneous generalized seizures. In the optic nerve, the fastest components of the compound action potential are slowed and the number of mature nodes of Ranvier is reduced, but Na sub(v)1.6, contactin, caspr 1, and K sub(v)1 channels are all localized normally at nodes. At the ultrastructural level, the paranodal septate-like junctions immediately adjacent to the node are missing in a subset of axons, suggesting that beta 1 may participate in axo-glial communication at the periphery of the nodal gap. Sodium currents in dissociated hippocampal neurons are normal, but Na sub(v)1.1 expression is reduced and Na sub(v)1.3 expression is increased in a subset of pyramidal neurons in the CA2/CA3 region, suggesting a basis for the epileptic phenotype. Our results show that beta 1 subunits play important roles in the regulation of sodium channel density and localization, are involved in axo-glial communication at nodes of Ranvier, and are required for normal action potential conduction and control of excitability in vivo.