Isoform-specific and pan-channel partners regulate trafficking and plasma membrane stability; and alter sodium channel gating properties.

Voltage-gated sodium channels are cell membrane glycoproteins responsible for action potential generation and propagation in excitable cells. These large polypeptides which are comprised of 24 transmembrane segments organized into four domains require cellular factors to regulate channel maturation and sorting to different cellular compartments, anchoring the channels at plasma membrane, and modulating gating properties of these channels as effector molecules in the signal transduction pathway. Mutations of sodium channels or their cytosolic partners produce similar pathologies, providing a compelling evidence for the biological significance of channel complexes that form during channel biogenesis and following sorting to different cellular compartments and anchoring at plasma membrane. Genetic, biochemical and bioinformatic approaches have been utilized to identify sodium channel partners. Here we review the important functional role of pan-sodium channel and isoform-specific partners in regulating sodium current density and gating properties.