Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles

OBJECTIVES This study was designed to determine whether ionic currents in right ventricular myocytes from explanted human transplant recipient hearts are related to right ventricular histopathology and function. BACKGROUND Cardiac action potential duration (APD) is prolonged in ventricular tissues/cells from patients with heart failure, but the ionic mechanisms are not well documented. METHODS Membrane currents and transmembrane action potentials in myocytes from right ventricular epicardium of explanted human hearts were recorded using whole-cell patch clamp technique. Data from cells from tight ventricles with severe histologic and functional abnormalities (abnormal histology group [AH]) and from right ventricles with preserved histology and function (relatively normal histology group [RNH]) were compared. RESULTS We found that APD at 50% (APD(50)) and 90% repolarization (APD(90)) were significantly longer in AH cells than in RNH cells. Early after depolarizations (EADs) were observed in 20% of AH cells and none of the RNH cells. Inwardly rectifying K+ current (I-Kl) was decreased (both inward and outward components). Both transient outward K+ current (I-tol) and slowly delayed rectifier K+ current (I-Ks.) were down-regulated in AH cells. L-type Ca2+ (I-Ca.L) was not altered in AH cells. CONCLUSIONS I-Kl, I-tol, and I-Ks are down-regulated in AH cells of human heart failure. This downregulation contributes to APD prolongation that favors the occurrence of arrhythmogenic EADs and suggests a link between human cardiac histooathologic/functional abnormalities and arrhythmogenic ionic remodeling.