Fozzard H A
Annu Rev Physiol. 1977;39:201-20. doi: 10.1146/annurev.ph.39.030177.001221.
The study of E-C coupling in heart muscle has been facilitated by the recent availability of reasonably reliable voltage clamp techniques and a method of "skinning" cardiac cells. We have also had the introduction of several new ideas, including a Na:Ca exchange pump, metabolically controlled Ca storage capacity of the SR, and length dependence of Ca release. Consideration of the mechanism of E-C coupling in striated muscle as a general model has enabled transfer of insights gained studying fast skeletal muscle to heart muscle. On the other hand, many of the complexities of regulation of heart muscle contraction are manifested in fast skeletal muscle, as investigators explore the details of E-C coupling. On the whole, it is interesting to be an investigator in this field, as the E-C coupling mechanisms under investigation are being located in many nonmuscle cells, for such varied functions as control of cell shape during growth and excitation-secretion coupling. The last few years have seen the establishment of the existence and importance of a channel in the membrane that admits Ca as a function of electric field. We remain uncertain, however, of the details of relation of this current to the size of contraction. We have begun to explore the characteristics and role of the Na:Ca exchange mechanism in regulating the magnitude of intracellular Ca stores. Most investigators feel that this finally represents the necessary link in understanding digitalis action. A powerful but technically demanding tool is available in the "skinned" cardiac cell, permitting direct studies of Ca release from the SR in more-or-less intact cells. One dramatic finding with that technique is the demonstration of length-dependence of Ca release. On the horizon are methods of monitoring any possible transient potentials across subcellular organelle membranes and directly determining transient changes in free Ca in the sarcoplasm. This reviewer cannot help but feel that the next three or four years will be exciting ones in this field, and that the next review of E-C coupling will make interesting reading.
近年来,相当可靠的电压钳技术以及心肌细胞“剥膜”方法的出现,推动了心肌兴奋-收缩偶联(E-C 偶联)的研究。我们还引入了一些新观点,包括钠-钙交换泵、肌浆网代谢控制的钙储存能力以及钙释放的长度依赖性。将横纹肌 E-C 偶联机制作为通用模型来考虑,使得从快速骨骼肌研究中获得的见解能够应用于心肌研究。另一方面,随着研究人员深入探究 E-C 偶联的细节,心肌收缩调节的许多复杂性也在快速骨骼肌中显现出来。总体而言,作为该领域的研究人员是很有趣的,因为正在研究的 E-C 偶联机制存在于许多非肌肉细胞中,具有诸如生长过程中细胞形状控制和兴奋-分泌偶联等多种功能。过去几年已经证实了细胞膜中存在一种随电场变化允许钙离子通过的通道及其重要性。然而,我们仍不确定该电流与收缩大小之间关系的细节。我们已开始探索钠-钙交换机制在调节细胞内钙储存量方面的特征和作用。大多数研究人员认为,这最终代表了理解洋地黄作用的必要环节。“剥膜”心肌细胞是一种强大但技术要求较高的工具,可用于在或多或少完整的细胞中直接研究肌浆网的钙释放。该技术的一个显著发现是证明了钙释放的长度依赖性。未来有望出现监测亚细胞器膜上任何可能的瞬态电位以及直接测定肌浆中游离钙瞬态变化的方法。这位审稿人不禁觉得,在这个领域接下来的三四年将会令人兴奋,而下一篇关于 E-C 偶联的综述将会很有意思。