Intracellular calcium attenuates late current conducted by mutant human cardiac sodium channels.

ABSTRACT:

Background

Mutations of the cardiac voltage-gated sodium channel (SCN5A gene encoding voltage-gated sodium channel [NaV1.5]) cause congenital long-QT syndrome type 3 (LQT3). Most NaV1.5 mutations associated with LQT3 promote a mode of sodium channel gating in which some channels fail to inactivate, contributing to increased late sodium current (INaL), which is directly responsible for delayed repolarization and prolongation of the QT interval. LQT3 patients have highest risk of arrhythmia during sleep or during periods of slow heart rate. During exercise (high heart rate), there is elevated steady-state intracellular free calcium (Ca(2+)) concentration. We hypothesized that higher levels of intracellular Ca(2+) may lower arrhythmia risk in LQT3 subjects through effects on INaL.

SUBMITTER: Potet F 

PROVIDER: S-EPMC4545406 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature