Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes.
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.


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.
Cell Physiology Laboratory, Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. lhove@hsp.santpau.es
Leif
L
Hove-Madsen
Anna
A
Llach
Antoni
A
Bayes-Genís
Santiago
S
Roura
Enrique
E
Rodriguez Font
Alejandro
A
Arís
Juan
J
Cinca
D000368:Aged; D020517:Atrial Appendage / Q000503:physiopathology / Q000648:ultrastructure; D001281:Atrial Fibrillation / Q000503:physiopathology*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D006325:Heart Atria / Q000503:physiopathology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D019831:Sodium-Calcium Exchanger