Hoshiyama Koki, Hara Motoki, Yasui Kenji, Mitamura Hideo, Ohsuzu Fumitaka, Kodama Itsuo, Ogawa Satoshi
Department of Medicine, Cardiology Division, Keio University School of Medicine, Tokyo, Japan.
Circ J. 2006 Nov;70(11):1488-96. doi: 10.1253/circj.70.1488.
Electrical instability following sustained rapid excitation has been attributed to altered ion channels. Alterations of Ca(2+) handling could also contribute to abnormal dynamics of action potential, favoring the initiation and perpetuation of arrhythmia.
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) Ca(2+) 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 Ca(2+) ATPase and SR Ca(2+)-release channel in RA was significantly reduced.
Altered Ca(2+) handling may underlie abnormal APD dynamics in RA.
持续快速兴奋后的电不稳定归因于离子通道改变。钙（Ca2+）处理的改变也可能导致动作电位的异常动态，促进心律失常的发生和持续。
记录正常犬（n = 6）和重构犬（以400次/分钟的频率进行6周心房起搏，n = 6）心房的跨膜动作电位和收缩力（TF）。当正常心房的心动周期长度（CL）突然延长时，TF和动作电位时程（APD）在第一个搏动时增加，随后降低。CL突然缩短时观察到相反的变化。APD和TF的这些动态变化被ryanodine消除，但被肌浆网（SR）Ca2+泵抑制剂环匹阿尼酸增强。在重构心房（RA）中，APD的动态变化也与TF的动态变化一致。与正常心房相比，APD和TF的短暂增加增强，短暂降低减少。RA中APD和TF恢复曲线的最大斜率更平坦，交替现象的幅度减小。RA中SR Ca2+ATP酶和SR Ca2+释放通道的蛋白表达显著降低。
Ca2+处理改变可能是RA中异常APD动态的基础。
