Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
Cell Calcium. 2012 Mar-Apr;51(3-4):309-20. doi: 10.1016/j.ceca.2011.12.004. Epub 2011 Dec 29.
The concept of stimulus-secretion coupling was born from experiments performed in chromaffin cells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca(2+)) entry and this generates a transient elevation of the cytosolic Ca(2+) concentration (Ca(2+)) that triggers the exocytotic release of catecholamines. The control of the Ca(2+) signal is complex and depends on various classes of plasmalemmal calcium channels, cytosolic calcium buffers, the uptake and release of Ca(2+) from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca(2+) extrusion mechanisms, such as the plasma membrane Ca(2+)-stimulated ATPase, and the Na(+)/Ca(2+) exchanger. Computation of the rates of Ca(2+) fluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca(2+) transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local Ca(2+) transients occurring at different cell compartments, and generated by redistribution and release of Ca(2+) by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo-endocytotic activities with energy production and protein synthesis.
刺激-分泌偶联的概念源于 50 年前对嗜铬细胞进行的实验。用乙酰胆碱刺激这些细胞可以增强钙（Ca(2+)）的内流，从而产生细胞质 Ca(2+)浓度(Ca(2+))的短暂升高，触发儿茶酚胺的胞吐释放。Ca(2+)信号的控制非常复杂，取决于各种类型的质膜钙通道、细胞质钙缓冲剂、细胞质细胞器（如内质网、线粒体、嗜铬小泡和核）中 Ca(2+)的摄取和释放，以及 Ca(2+)外排机制，如质膜 Ca(2+)-ATP 酶和 Na(+)/Ca(2+)交换体。对不同细胞区室之间 Ca(2+)通量速率的计算支持了这样一种观点，即嗜铬细胞已经发展出功能性的钙四联体，由钙通道、细胞质钙缓冲剂、内质网和附近质膜胞吐部位的线粒体组成。这些四联体形成了细胞激活过程中发生的 Ca(2+)瞬变，以调节胞吐的早期和晚期步骤以及随后的内吞反应。因此，对应激的不同儿茶酚胺分泌模式可能取决于不同细胞区室中发生的局部Ca(2+)瞬变，这些瞬变是由细胞质细胞器的重分布和 Ca(2+)释放产生的。通过这种方式，钙四联体将由于外排-内吞活动引起的可变能量需求与能量产生和蛋白质合成联系起来。
