| Description: |
The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more non-pore-forming beta subunits. There are five different beta-subunit proteins (beta-1, beta-1B, beta-2, beta-3, and beta-4) encoded by four genes (SCN1B-SCN4B; beta-1B is a splice variant of SCN1B) [, ]. Beta-subunits modulate the kinetics and voltage dependence of the alpha-subunits and they also affect the voltage-gated potassium channels. These subunits participate in nonconducting roles, including cell-cell and cell-matrix adhesion, directing neuronal proliferation, migration, and fasciculation, and modulating the effects of pharmacological compounds on voltage-gated sodium channels, playing important roles in development and disease [, ].Subunit beta-1 is crucial in the assembly, expression, and functional modulation of the sodium channel that can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart [, ]. Both beta-1 and beta-3 associate with neurofascin through their extracellular immunoglobulin-like domains. This association may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons [].This family represents the beta-1 subunit which modulates the activity of multiple pore-forming alpha subunits, such as SCN1A, SCN2A, SCN3A, SCN4A, SCN5A and SCN10A. It plays a critical role in neuronal migration and pathfinding during brain development, and its function is dependent on Na+ current and gamma-secretase activity [, ]. Alterations in this subunit cause epilepsy and cardiac arrhythmia []. Deletion of SCN1B results in Dravet Syndrome, a severe pediatric encephalopathy characterised by epilepsy development [, ]. The D25N mutation in this subunit causes generalised epilepsy with febrile seizure plus type 1 (GEFS+), leading to a maturation (glycosylation) defect of the protein which impairs its targeting to the plasma membrane and interaction with alpha subunits [, ]. |
