Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes

Abstract
Background— Spontaneous Ca 2+ 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 Ca 2+ release and initiation of atrial fibrillation (AF), but this has not yet been reported. Methods and Results— Spontaneous Ca 2+ release from the SR, manifested as Ca 2+ sparks and Ca 2+ 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 Ca 2+ waves was measured with the use of the perforated patch-clamp technique. The Ca 2+ 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 2+ wave frequency was greater in patients with AF (2.8±0.5 versus 1.1±0.3 waves/mm per second, P P 2+ released from the SR and the Na + -Ca 2+ exchange rate induced by a rapid caffeine application were comparable in patients with and without AF. Conclusions— The observed increase in spontaneous Ca 2+ release in patients with AF probably is due to an upregulation of the SR Ca 2+ release channel activity, which may contribute to the development of AF.