Calcium-mediated dual-mode regulation of cardiac sodium channel gating.

ABSTRACT: Intracellular Ca(2+) ([Ca(2+)](i)) can trigger dual-mode regulation of the voltage gated cardiac sodium channel (Na(V)1.5). The channel components of the Ca(2+) regulatory system are the calmodulin (CaM)-binding IQ motif and the Ca(2+) sensing EF hand-like (EFL) motif in the carboxyl terminus of the channel. Mutations in either motif have been associated with arrhythmogenic changes in expressed Na(V)1.5 currents. Increases in [Ca(2+)](i) shift the steady-state inactivation of Na(V)1.5 in the depolarizing direction and slow entry into inactivated states. Mutation of the EFL (Na(V)1.5(4X)) shifts inactivation in the hyperpolarizing direction compared with the wild-type channel and eliminates the Ca(2+) sensitivity of inactivation gating. Modulation of the steady-state availability of Na(V)1.

SUBMITTER: Biswas S 

PROVIDER: S-EPMC2860428 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature