A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated Na ⁺ Channels.

ABSTRACT: Fast Inactivation in voltage-gated Na ⁺ channels plays essential roles in numerous physiological functions. The canonical hinged-lid model has long predicted that a hydrophobic motif in the DIII-DIV linker (IFM) acts as the gating particle that occludes the permeation pathway during fast inactivation. However, the fact that the IFM motif is located far from the pore in recent high-resolution structures of Nav ⁺ channels contradicts this status quo model. The precise molecular determinants of fast inactivation gate once again, become an open question. Here, we provide a mechanistic reinterpretation of fast inactivation based on ionic and gating current data. In Nav1.4 the actual inactivation gate is comprised of two hydrophobic rings at the bottom of S6.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC10168311 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature