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


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 Ca(2+) sparks, spark full duration, time to peak Ca(2+) 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,L) current densities. Candesartan blocked these ANG II-mediated alterations. ANG II exhibited no effect on I(K1), 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.


CONCLUSIONS
ANG 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.
Gassanov
Natig
N
Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, Cologne 50937, Germany.
Brandt
Mathias C
MC
Michels
Guido
G
Lindner
Michael
M
Er
Fikret
F
Hoppe
Uta C
UC
D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000097:blood / Q000209:etiology* / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D000097003:Gap Junction alpha-5 Protein
D000804:Angiotensin II; D018031:Connexin 43; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; C500216:GJA1 protein, human