Structural mechanism of voltage-gated sodium channel slow inactivation.

ABSTRACT: Voltage-gated sodium (Na_V) channels mediate a plethora of electrical activities. Na_V channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of Na_V channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying Na_V channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of Na_VEh (Na_VEh^ΔN) results in a slow-inactivated channel, and present cryo-EM structure of Na_VEh^ΔN in a potential slow-inactivated state.

SUBMITTER: Chen H 

PROVIDER: S-EPMC11063143 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature