Tweedie D, Harding S E, MacLeod K T
Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, UK.
J Mol Cell Cardiol. 2000 Feb;32(2):261-72. doi: 10.1006/jmcc.1999.1070.
Early afterdepolarizations are seen during the repolarization phases of the action potential and delayed afterdepolarizations appear later, usually following complete repolarization of the cell membrane potential. Both forms of afterdepolarization are linked to the occurrence of aftercontractions, seem to play a role in the generation of ventricular arrhythmias and are believed to be the result of abnormalities of intracellular Ca handling. Suggestions for the mechanisms responsible vary from both types of afterpotential being mediated by Ca release from the sarcoplasmic reticulum, to early afterdepolarization formation being due to reactivation of the L-type sarcolemmal Ca channels during the action potential. We tried to assess the functional importance of the sarcoplasmic reticulum or Ca influx in the development of afterpotentials and abnormal contractile activity in guinea-pig cardiac myocytes. Ca influx was increased using isoproterenol, Bay K8644 or increasing extracellular [Ca]. Sarcoplasmic reticulum Ca content was measured using rapid cooling contractures or caffeine-induced Na/Ca exchange current and the sarcoplasmic reticulum was inhibited using caffeine or thapsigargin. Aftercontractions associated with either early or delayed afterdepolarizations could be induced by increasing Ca influx. The increased Ca influx produced increases in sarcoplasmic reticulum Ca content and aftercontractions were associated with a larger SR Ca content. However, the sarcoplasmic reticulum was no more loaded with Ca when aftercontractions occurred than when aftercontractions did not occur. Preventing Ca sequestration by the sarcoplasmic reticulum inhibited the formation of aftercontractions. The results suggest that alterations to both Ca influx and sarcoplasmic reticulum Ca content are required to produce aftercontractions.
早期后去极化出现在动作电位的复极化阶段，而延迟后去极化出现得较晚，通常在细胞膜电位完全复极化之后。这两种形式的后去极化都与后收缩的发生有关，似乎在室性心律失常的产生中起作用，并且被认为是细胞内钙处理异常的结果。关于其机制的推测各不相同，从两种类型的后电位均由肌浆网释放钙介导，到早期后去极化的形成是由于动作电位期间L型肌膜钙通道的再激活。我们试图评估肌浆网或钙内流在豚鼠心肌细胞后电位发展及异常收缩活动中的功能重要性。使用异丙肾上腺素、Bay K8644或增加细胞外[Ca]来增加钙内流。使用快速冷却挛缩或咖啡因诱导的钠/钙交换电流来测量肌浆网钙含量，并使用咖啡因或毒胡萝卜素抑制肌浆网。增加钙内流可诱导与早期或延迟后去极化相关的后收缩。钙内流增加导致肌浆网钙含量增加，后收缩与更大的肌浆网钙含量相关。然而，出现后收缩时肌浆网的钙负荷并不比未出现后收缩时更高。阻止肌浆网对钙的摄取可抑制后收缩的形成。结果表明，产生后收缩需要钙内流和肌浆网钙含量的改变。
