Mice lacking sodium channel β1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture

C Chen, RE Westenbroek, X Xu… - Journal of …, 2004 - Soc Neuroscience
C Chen, RE Westenbroek, X Xu, CA Edwards, DR Sorenson, Y Chen, DP McEwen…
Journal of Neuroscience, 2004Soc Neuroscience
Sodium channel β1 subunits modulate α subunit gating and cell surface expression and
participate in cell adhesive interactions in vitro. β1 (-/-) 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 Nav1. 6, contactin, caspr 1, and Kv1 channels are all localized normally at
nodes. At the ultrastructural level, the paranodal septate-like junctions immediately adjacent …
Sodium channel β1 subunits modulate α subunit gating and cell surface expression and participate in cell adhesive interactions in vitro. β1(-/-) 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 Nav1.6, contactin, caspr 1, and Kv1 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 β1 may participate in axo-glial communication at the periphery of the nodal gap. Sodium currents in dissociated hippocampal neurons are normal, but Nav1.1 expression is reduced and Nav1.3 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 β1 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.
Soc Neuroscience