Electrophysiology and beyond: multiple roles of Na+ channel β subunits in development and disease.
Voltage-gated Na+ channel (VGSC) β 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. β 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 β subunit cell adhesive functions occur both in the presence and absence of pore-forming VGSC α subunits, and in vivo β subunits are expressed in excitable as well as non-excitable cells, thus β subunits may play important functional roles on their own, in the absence of α subunits. VGSC β1 subunits are essential for life and appear to be especially important during brain development. Mutations in β subunit genes result in a variety of human neurological and cardiovascular diseases. Moreover, some cancer cells exhibit alterations in β subunit expression during metastasis. In short, these proteins, originally thought of as merely accessory to α subunits, are critical players in their own right in human health and disease. Here we discuss the role of VGSC β subunits in the nervous system.
Patino
Gustavo A
GA
Department of Pharmacology and Neuroscience Program, University of Michigan, Ann Arbor, MI 48109, United States.
Isom
Lori L
LL
D000818:Animals; D001369:Axons / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D015815:Cell Adhesion Molecules; D021122:Protein Subunits; D015222:Sodium Channels