Published online before print August 16, 2004, doi: 10.1161/01.CIR.0000141296.59876.87
(Circulation. 2004;110:1358-1363.)
© 2004 American Heart Association, Inc.
Original Articles |
Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes
From the Cell Physiology Laboratory, Department of Cardiology (L.H.-M., A.L., A.B.-G., S.R., E.R.F., J.C.) and the Department of Cardiac Surgery (A.A.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Correspondence to Leif Hove-Madsen, Servei de Cardiología, Hospital de la Santa Creu i Sant Pau, St Antoni Ma Claret 167, 08025 Barcelona, Spain. E-mail lhove{at}hsp.santpau.es
Received February 18, 2004; revision received April 29, 2004; accepted April 30, 2004.
Background— Spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) can generate afterdepolarizations, and these have the potential to initiate arrhythmias. Therefore, an association may exist between spontaneous SR Ca2+ release and initiation of atrial fibrillation (AF), but this has not yet been reported.
Methods and Results— Spontaneous Ca2+ release from the SR, manifested as Ca2+ sparks and Ca2+ waves, was recorded with confocal microscopy in atrial myocytes isolated from patients with and those without AF. In addition, the spontaneous inward current associated with Ca2+ waves was measured with the use of the perforated patch-clamp technique. The Ca2+ spark frequency was higher in 8 patients with AF than in 16 patients without (6.0±1.2 versus 2.8±0.8 sparks/mm per second, P<0.05). Similarly, the spontaneous Ca2+ wave frequency was greater in patients with AF (2.8±0.5 versus 1.1±0.3 waves/mm per second, P<0.01). The spontaneous inward current frequency was also higher in 10 patients with AF than in 13 patients without this arrhythmia (0.101±0.028 versus 0.031±0.007 per second, P<0.05, at a clamped potential of –80 mV). In contrast, both the Ca2+ released from the SR and the Na+-Ca2+ exchange rate induced by a rapid caffeine application were comparable in patients with and without AF.
Conclusions— The observed increase in spontaneous Ca2+ release in patients with AF probably is due to an upregulation of the SR Ca2+ release channel activity, which may contribute to the development of AF.
Key Words: sarcoplasmic reticulum • calcium • arrhythmia • ion channels • electrophysiology
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