Probing noncanonical coupling between voltage sensor domains and pore domains in voltage-gated sodium channels

Abstract

Understanding the functional mechanisms of mammalian voltage gated sodium channels (NaVs) is critical, because they are crucial in action potential generation. Recent work in voltage-gated potassium channels (KVs) has revealed that the voltage sensing domains (VSDs) and the pore domains (PDs) communicate through noncanonical coupling mechanisms, which are based on noncovalent interactions. Structurally, several KVs and isoforms of mammalian NaVshare a topology termed the domain-swapped assembly.