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

Gui-Rong Li·Chu-Pak Lau·Tack-Ki Leung·Stanley Nattel
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Abstract

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 right 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 afterdepolarizations (EADs) were observed in 20% of AH cells and none of the RNH cells. Inwardly rectifying K(+) current (I(K1)) was decreased (both inward and outward components). Both transient outward K(+) current (I(to1)) and slowly delayed rectifier K(+) current (I(Ks)) were down-regulated in AH cells. L-type Ca(2+) (I(Ca.L)) was not altered in AH cells. CONCLUSIONS: I(K1), I(to1), and I(Ks) are down-regulated in AH cells of human heart failure. This down-regulation contributes to APD prolongation that favors the occurrence of arrhythmogenic EADs and suggests a link between human cardiac histopathologic/functional abnormalities and arrhythmogenic ionic remodeling.

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Action PotentialsAdultAgedCalciumCalcium Channels, L-TypeElectrophysiologic Techniques, CardiacHeart VentriclesHumansIn Vitro TechniquesIon Channel GatingMembrane PotentialsMiddle AgedMyocytes, CardiacPotassium Channels, Voltage-GatedTime FactorsTransplantationVentricular Dysfunction, RightComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Gui-Rong Li, Chu-Pak Lau, Tack-Ki Leung, Stanley Nattel. 2004. Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles.. https://doi.org/10.1016/j.hrthm.2004.06.003

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