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

Aims: Atrial 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 results: Isolated 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 I-to and increased I-Ca,I-L current densities. Candesartan blocked these ANG II-mediated alterations. ANG II exhibited no effect on I-KI, I-Kur and I-f current size. Expression of connexin 40 and connexin 43 was not significantly changed by ANG II as assessed by immunohistochemistry and Western blot analysis. Conclusion: ANG II-induced alterations of calcium handling and electrophysiological changes inhuman 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. (C) 2005 Elsevier Ltd. All rights reserved.