Synchronous systolic subcellular Ca2+-elevations underlie ventricular arrhythmia in drug-induced long QT type 2.

ABSTRACT:

Background

Repolarization delay is a common clinical problem, which can promote ventricular arrhythmias. In myocytes, abnormal sarcoplasmic reticulum Ca(2+)-release is proposed as the mechanism that causes early afterdepolarizations, the cellular equivalent of ectopic-activity in drug-induced long-QT syndrome. A crucial missing link is how such a stochastic process can overcome the source-sink mismatch to depolarize sufficient ventricular tissue to initiate arrhythmias.

Methods and results

Optical maps of action potentials and Ca(2+)-transients from Langendorff rabbit hearts were measured at low (150×150 μm(2)/pixel) and high (1.5×1.5 μm(2)/pixel) resolution before and during arrhythmias. Drug-induced long QT type 2, elicited with dofetilide inhibition of IKr (the rapid comp

SUBMITTER: Kim JJ 

PROVIDER: S-EPMC4472565 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature