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.
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.
Authors: David Y Chiang; Na Li; Qiongling Wang; Katherina M Alsina; Ann P Quick; Julia O Reynolds; Guoliang Wang; Darlene Skapura; Niels Voigt; Dobromir Dobrev; Xander H T Wehrens Journal: Cardiovasc Res Date: 2014-05-08 Impact factor: 10.787
Authors: Mihail G Chelu; Satyam Sarma; Subeena Sood; Sufen Wang; Ralph J van Oort; Darlene G Skapura; Na Li; Marco Santonastasi; Frank Ulrich Müller; Wilhelm Schmitz; Ulrich Schotten; Mark E Anderson; Miguel Valderrábano; Dobromir Dobrev; Xander H T Wehrens Journal: J Clin Invest Date: 2009-07 Impact factor: 14.808