Open-state structure and pore gating mechanism of the cardiac sodium channel

Abstract

Voltage-gated sodium (Nav) channels open to initiate the action potential in excitable cells, then close within a few milliseconds via fast inactivation. Rapid opening and fast inactivation focus the depolarizing stimulus of the cardiac action potential and support the rapid and efficient conduction needed for a regular heartbeat. Fast inactivation is disrupted by mutations in the DIII/DIV linker of Nav channels, including mutations in the canonical IFM motif (isoleucine/phenylalanine/ methionine) of the “fast inactivation particle” .