Structural basis of human Na_v1.5 gating mechanisms.

ABSTRACT: Voltage-gated Na_v1.5 channels are central to the generation and propagation of cardiac action potentials. Aberrations in their function are associated with a wide spectrum of cardiac diseases including arrhythmias and heart failure. Despite decades of progress in Na_v1.5 biology, the lack of structural insights into intracellular regions has hampered our understanding of its gating mechanisms. Here, we present two cryo-EM structures of human Na_v1.5 in open states, revealing sequential conformational changes in gating charges of the voltage-sensing domains (VSDs) and several intracellular regions. Despite the channel being in the open state, these structures show repositioning, but no dislodging of the IFM motif in the receptor site. Molecular dynamics analys

SUBMITTER: Biswas R 

PROVIDER: S-EPMC12107192 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature