The voltage-gated sodium channel pore exhibits conformational flexibility during slow inactivation.

ABSTRACT: Slow inactivation in voltage-gated sodium channels (Na_Vs) directly regulates the excitability of neurons, cardiac myocytes, and skeletal muscles. Although Na_V slow inactivation appears to be conserved across phylogenies-from bacteria to humans-the structural basis for this mechanism remains unclear. Here, using site-directed labeling and EPR spectroscopic measurements of membrane-reconstituted prokaryotic Na_V homologues, we characterize the conformational dynamics of the selectivity filter region in the conductive and slow-inactivated states to determine the molecular events underlying Na_V gating. Our findings reveal profound conformational flexibility of the pore in the slow-inactivated state. We find that the P1 and P2 pore helices undergo oppo

SUBMITTER: Chatterjee S 

PROVIDER: S-EPMC6122925 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature