NCX-Mediated Subcellular Ca²⁺ Dynamics Underlying Early Afterdepolarizations in LQT2 Cardiomyocytes.

ABSTRACT: Long QT syndrome type 2 (LQT2) is a congenital disease characterized by loss of function mutations in hERG potassium channels (I_Kr). LQT2 is associated with fatal ventricular arrhythmias promoted by triggered activity in the form of early afterdepolarizations (EADs). We previously demonstrated that intracellular Ca²⁺ handling is remodeled in LQT2 myocytes. Remodeling leads to aberrant late RyR-mediated Ca²⁺ releases that drive forward-mode Na⁺-Ca²⁺ exchanger (NCX) current and slow repolarization to promote reopening of L-type calcium channels and EADs. Forward-mode NCX was found to be enhanced despite the fact that these late releases do not significantly alter the whole-cell cytosolic calcium concentration during a vulnerable period o

SUBMITTER: Zhong M 

PROVIDER: S-EPMC6140381 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature