Voltage-gated sodium channels as therapeutic targets

Voltage-gated sodium channels (VGSCs) play a central role in the generation and propagation of action potentials in neurons and other cells. VGSC modu lators have their origins in empirical pharmacology and are being used as l ocal anaesthetics, antiarrhythmics, analgesics and antiepileptics, and for other disorders. However, the identification of a multigene family of VGSCs , along with tools to study the different subtypes in pathophysiology, is n ow providing a rational basis for selective intervention. Recent advances h ave addressed the technical challenges of expressing and assaying these com plex proteins, enabling the correlation of empirical pharmacology to subtyp es and the screening of individual subtypes for novel inhibitors with incre ased potency and selectivity.