Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors.

ABSTRACT: Voltage-gated sodium channels (Nav) underlie the electrical activity of nerve and muscle cells. Humans have nine different subtypes of these channels, which are the target of small-molecule inhibitors commonly used to treat a range of conditions. Structural studies have identified four lateral fenestrations within the Nav pore module that have been shown to influence Nav pore blocker access during resting-state inhibition. However, the structural differences among the nine subtypes are still unclear. In particular, the dimensions of the four individual fenestrations across the Nav subtypes and their differential accessibility to pore blockers is yet to be characterized. To address this, we applied classical molecular dynamics simulations to study the recently published structures of Nav1.1

SUBMITTER: Tao E 

PROVIDER: S-EPMC8790208 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature