Angiotensin II-induced changes of calcium sparks and ionic currents in human atrial myocytes: Potential role for early remodeling in atrial fibrillation

AimsAtrial angiotensin II (ANG II) levels have been shown to be increased in atrial fibrillation (AF). The purpose of the study was to evaluate a potential role of ANG II in the early remodeling and susceptibility to chronicization of AF.Methods and resultsIsolated human atrial myocytes were incubated in ANG II and/or angiotensin type 1 receptor blocker candesartan. ANG II markedly increased the frequency of spontaneous Ca2+ sparks, spark full duration, time to peak Ca2+ fluorescence and decay time measured by confocal imaging. Sarcoplasmic reticulum calcium content estimated by caffeine-evoked calcium release did not differ between ANG II-treated cells and controls. Patch-clamp recordings revealed that ANG II significantly decreased Ito and increased ICa,L current densities. Candesartan blocked these ANG II-mediated alterations. ANG II exhibited no effect on IK1, IKur and If current size. Expression of connexin 40 and connexin 43 was not significantly changed by ANG II as assessed by immunohistochemistry and Western blot analysis.ConclusionANG II-induced alterations of calcium handling and electrophysiological changes in human atrial cells similar to those previously observed in the onset of AF. Prevention of these alterations by candesartan might constitute a useful pharmacological strategy for the treatment of AF.