Mining Protein Evolution for Insights into Mechanisms of Voltage-Dependent Sodium Channel Auxiliary Subunits.

Voltage-gated sodium channel (VGSC) beta (β) subunits have been called the "overachieving" auxiliary ion channel subunit. Indeed, these subunits regulate the trafficking of the sodium channel complex at the plasma membrane and simultaneously tune the voltage-dependent properties of the pore-forming alpha-subunit. It is now known that VGSC β-subunits are capable of similar modulation of multiple isoforms of related voltage-gated potassium channels, suggesting that their abilities extend into the broader voltage-gated channels.

Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel.

Voltage-gated, sodium ion-selective channels (Na) generate electrical signals contributing to the upstroke of the action potential in animals. Nas are also found in bacteria and are members of a larger family of tetrameric voltage-gated channels that includes Cas, Ks, and Nas. Prokaryotic Nas likely emerged from a homotetrameric Ca-selective voltage-gated progenerator, and later developed Na selectivity independently.