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.