Altered Na+ channels promote pause-induced spontaneous diastolic activity in long QT syndrome type 3 myocytes.

ABSTRACT: Long QT syndrome (LQTS) type 3 (LQT3), typified by the DeltaKPQ mutation (LQT3 mutation in which amino acid residues 1505 to 1507 [KPQ] are deleted), is caused by increased sodium entry during the action potential plateau resulting from mutation-altered inactivation of the Na(v)1.5 channel. Although rare, LQT3 is the most lethal of common LQTS variants. Here we tested the hypothesis that cellular electrical dysfunction, caused not only by action potential prolongation but also by mutation-altered Na(+) entry, distinguishes LQT3 from other LQTS variants and may contribute to its distinct lethality. We compared cellular electrical activity in myocytes isolated from mice heterozygous for the DeltaKPQ mutation (DeltaKPQ) and myocytes from wild-type littermates. Current-clamp pause protocols in

SUBMITTER: Fredj S 

PROVIDER: S-EPMC4454351 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature