Fabiato A
J Gen Physiol. 1985 Feb;85(2):291-320. doi: 10.1085/jgp.85.2.291.
Skinned canine cardiac Purkinje cells were stimulated by regularly repeated microinjection-aspiration sequences that were programmed to simulate the fast initial component of the transsarcolemmal Ca2+ current and the subsequent slow component corresponding to noninactivating Ca2+ channels. The simulated fast component triggered a tension transient through Ca2+-induced release of Ca2+ from the sarcoplasmic reticulum (SR). The simulated slow component did not affect the tension transient during which it was first introduced but it potentiated the subsequent transients. The potentiation was not observed when the SR function had been destroyed by detergent. The potentiation decreased progressively when the slow component was separated by an increasing time interval from the fast component. The potentiation was progressive over several beats under conditions that decreased the rate of Ca2+ accumulation into the SR (deletion of calmodulin from the solutions; a decrease of the temperature from 22 to 12 degrees C). In the presence of a slow component, an increase of frequency caused a positive staircase, and the introduction of an extrasystole caused a postextrasystolic potentiation. There was a negative staircase and no postextrasystolic potentiation in the absence of a slow component. These results can be explained by a time- and Ca2+-dependent functional separation of the release and accumulation processes of the SR, rather than by Ca2+ circulation between anatomically distinct loading and release compartments. The fast initial component of transsarcolemmal Ca2+ current would trigger Ca2+ release, whereas the slow component would load the SR with an amount of Ca2+ available for release during the subsequent tension transients.
通过定期重复的微量注射-抽吸序列刺激去表皮犬心脏浦肯野细胞,该序列经编程以模拟跨肌膜Ca2+电流的快速初始成分以及对应于非失活Ca2+通道的后续缓慢成分。模拟的快速成分通过Ca2+诱导肌浆网(SR)释放Ca2+触发张力瞬变。模拟的缓慢成分在首次引入时不影响张力瞬变,但会增强随后的瞬变。当SR功能被去污剂破坏时未观察到增强作用。当缓慢成分与快速成分之间的时间间隔增加时,增强作用逐渐减弱。在降低Ca2+积累到SR中的速率的条件下(从溶液中删除钙调蛋白;温度从22℃降至12℃),增强作用在几个心动周期中是渐进的。在存在缓慢成分的情况下,频率增加会导致正阶梯现象,而早搏的引入会导致早搏后增强。在不存在缓慢成分的情况下,会出现负阶梯现象且无早搏后增强。这些结果可以通过SR释放和积累过程的时间和Ca2+依赖性功能分离来解释,而不是通过解剖学上不同的装载和释放区室之间的Ca2+循环来解释。跨肌膜Ca2+电流的快速初始成分会触发Ca2+释放,而缓慢成分会在随后的张力瞬变期间向SR加载可用于释放的一定量Ca2+。