Abstract
Background Electrical instability following sustained rapid excitation has been attributed to altered ion channels. Alterations of Ca2+ handling could also contribute to abnormal dynamics of action potential, favoring the initiation and perpetuation of arrhythmia. Methods and Results Transmembrane action potentials and twitch force (TF) were recorded from normal (n=6) and remodeled (6-week atrial pacing at 400 beats/min, n=6) canine atria. When the cycle length (CL) was suddenly prolonged in normal atria, both TF and action potential duration (APD) increased on the first beat, and decreased subsequently. Opposite changes were observed with sudden CL shortening. These dynamics in both APD and TF were abolished by ryanodine, but augmented by cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump. In remodeled atria (RA), dynamic changes in APD were also concordant with dynamic changes in TF. The transient increases in APD and TF were enhanced, and the transient decreases were reduced compared to normal atria. The maximal slopes of APD and TF restitution curves were flatter and the magnitude of alternans was reduced in RA. The protein expression of SR Ca2+ ATPase and SR Ca2+-release channel in RA was significantly reduced. Conclusion Altered Ca2+ handling may underlie abnormal APD dynamics in RA. (Circ J 2006; 70: 1488 - 1496)
