Grantham C J, Cannell M B
Department of Pharmacology, St. George's Hospital Medical School, London, UK.
Circ Res. 1996 Aug;79(2):194-200. doi: 10.1161/01.res.79.2.194.
The relative contributions of L-type Ca2+ current (ICa) and Na+/Ca2+ exchange to Ca2+ influx during the cardiac action potential (AP) are unknown. In this study, we have used an AP recorded under physiological conditions as the command voltage applied to voltage-clamped ventricular myocytes. ICa (measured as nifedipine-sensitive membrane current) had a complex multiphasic time course during the AP. Peak ICa was typically 4 pA/pF, after which it rapidly declined (to about 60% of peak) during the rising phase of the cell-wide Ca2+ transient before increasing to a second, more sustained component. The initial decline in ICa was sensitive to the amount of Ca2+ released by the sarcoplasmic reticulum (SR), and conditions that reduce the amplitude of the Ca2+ transient (such as rest or brief application of caffeine) increased net Ca2+ influx via ICa. Dissection of the Na+/Ca2+ exchange current at the start of the AP suggested that Ca2+ influx via Na+/Ca2+ exchange is less than 30% of that due to ICa. From these data, we suggest that ICa is the primary source of Ca2+ that triggers SR Ca2+ release, even at the highly depolarized membrane potentials associated with the AP. However, Ca2+ influx via Na+/Ca2+ exchange is not negligible and may activate some Ca2+ release from the SR, especially when ICa is reduced. We propose that SR Ca2+ release inhibits ICa within the same beat, thereby providing a negative feedback mechanism that may serve to limit Ca2+ influx as well as to regulate the amount of Ca2+ stored within the SR.
在心脏动作电位（AP）期间，L型钙电流（ICa）和钠钙交换对钙内流的相对贡献尚不清楚。在本研究中，我们将生理条件下记录的AP用作施加于电压钳制心室肌细胞的指令电压。ICa（以硝苯地平敏感膜电流测量）在AP期间具有复杂的多相时程。ICa峰值通常为4 pA/pF，之后在全细胞钙瞬变的上升期迅速下降（至峰值的约60%），然后增加到第二个更持久的成分。ICa的初始下降对肌浆网（SR）释放的钙量敏感，降低钙瞬变幅度的条件（如静息或短暂应用咖啡因）会增加通过ICa的净钙内流。在AP开始时对钠钙交换电流的分析表明，通过钠钙交换的钙内流小于ICa所致钙内流的30%。根据这些数据，我们认为ICa是触发SR钙释放的主要钙来源，即使在与AP相关的高度去极化膜电位下也是如此。然而，通过钠钙交换的钙内流并非可以忽略不计，并且可能激活SR的一些钙释放，尤其是当ICa降低时。我们提出，SR钙释放在同一心动周期内抑制ICa，从而提供一种负反馈机制，该机制可能有助于限制钙内流以及调节SR内储存的钙量。
