Electrophysiology and beyond: Multiple roles of Na+ channel β subunits in development and disease

Voltage-gated Na+ channel (VGSC) beta Subunits are not "auxiliary." These multi-functional molecules not only modulate Na+ current (I-NA), but also function as cell adhesion molecules (CAMs) playing roles in aggregation, migration, invasion, neurite outgrowth, and axonal fasciculation. beta subunits are integral members of VGSC signaling complexes at nodes of Ranvier, axon initial segments, and cardiac intercalated disks, regulating action potential propagation through critical intermolecular and cell-cell communication events. At least in vitro, many beta subunit cell adhesive functions occur both in the presence and absence of pore-forming VGSC to subunits, and in vivo beta subunits are expressed in excitable as well as non-excitable cells, thus beta subunits may play important functional roles on their own, in the absence of a subunits. VGSC beta subunits are essential for life and appear to be especially important during brain development. Mutations in beta subunit genes result in a variety of human neurological and cardiovascular diseases. Moreover, some cancer cells exhibit alterations in beta subunit expression during metastasis. In short, these proteins, originally thought of as merely accessory to alpha subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC beta subunits in the nervous system. (C) 2010 Elsevier Ireland Ltd. All rights reserved.