Closed-state inactivation of cardiac, skeletal, and neuronal sodium channels is isoform specific.

ABSTRACT: Voltage-gated sodium (Nav) channels produce the upstroke of action potentials in excitable tissues throughout the body. The gating of these channels is determined by the asynchronous movements of four voltage-sensing domains (VSDs). Past studies on the skeletal muscle Nav1.4 channel have indicated that VSD-I, -II, and -III are sufficient for pore opening, whereas VSD-IV movement is sufficient for channel inactivation. Here, we studied the cardiac sodium channel, Nav1.5, using charge-neutralizing mutations and voltage-clamp fluorometry. Our results reveal that both VSD-III and -IV are necessary for Nav1.5 inactivation, and that steady-state inactivation can be modulated by all VSDs. We also demonstrate that channel activation is partially determined by VSD-IV movement. Kinetic modeling sugg

SUBMITTER: Brake N 

PROVIDER: S-EPMC9136305 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature