Smith J B
Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham 35294-0019, USA.
New Horiz. 1996 Feb;4(1):2-18.
Calcium triggers muscle contraction and is a second messenger of hormones and growth factors that regulate metabolism, gene expression, and secretion in smooth muscle cells (SMC). SMC contain dozens of proteins that bind Ca2+ either to buffer changes in ionized calcium or to elicit a cellular response such contraction or secretion. Although there practically an infinite supply of Ca2+ in extracellular medium, SMC respond to a variety of stimuli by mobilizing Ca2+ accumulated in the sarcoplasmic reticulum (SR), where most cellular Ca2+ resides. The SR of smooth muscle resembles the endoplasmic reticulum of nonmuscle cells and accumulates Ca2+ via the sarcoendoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase). Stimuli, such as angiotensin II, produce inositol 1,4,5,-trisphosphate (IP3), which regulates a Ca2+ channel of the SR. IP3 binding opens the channel and produces a "spike" in the cytoplasmic concentration of free Ca2+ ([Ca2+]i). The spike is largely due to the release of stored Ca2+ because hormonal stimulation produces similar spikes in the presence and absence of extracellular Ca2+. Ca2+ ejection from the cell, rather than reaccumulation by the SR, is responsible for rapidly decreasing [Ca2+]i from the peak level produced by the stimulus. Release of SR Ca2+ and activation of plasma membrane Ca2+ efflux mechanisms markedly decrease total cell Ca2+. Two independent Ca2+ transporters in the plasma membrane, the Na(+)-Ca2+ exchanger and the Ca2+ ATPase, actively eject Ca2+ from SMC. The Na(+)-Ca2+ exchanger is largely responsible for the acute phase of Ca2+ ejection, whereas the plasma membrane Ca2+ ATPase contributes to the sustained increase in Ca2+ efflux from stimulated SMC. Following Ca2+ release from the SR and ejection from the cell, Ca2+ enters via channels, which sustain a modest increase in [Ca2+]i and a gradual refilling of the SR. Mitochondria have an important role in intracellular Ca2+ signaling. Mitochondrial metabolism is highly responsive to transient increases in [Ca2+]i, although mitochondria are not a Ca2+ repository. Ca2+ uptake by mitochondria is driven by the highly favorable electrochemical potential difference across the inner membrane. Mitochondria actively expel Ca2+ via a H(+)-Ca2+ or Na(+)-Ca2+ exchanger. Ca2+ uptake and ejection by mitochondria contributes to temporal and spatial oscillations in [Ca2+]i. accelerated Ca2+ cycling between the Sr, cytoplasm, mitochondria, and the environment is a hallmark of cell stimulation.
钙触发肌肉收缩，并且是调节平滑肌细胞（SMC）新陈代谢、基因表达和分泌的激素及生长因子的第二信使。SMC含有数十种结合Ca2+的蛋白质，这些蛋白质要么缓冲游离钙离子的变化，要么引发诸如收缩或分泌等细胞反应。尽管细胞外介质中实际上有无限供应的Ca2+，但SMC通过动员积累在肌浆网（SR）中的Ca2+对多种刺激做出反应，大多数细胞内Ca2+都存在于SR中。平滑肌的SR类似于非肌肉细胞的内质网，并通过肌浆网Ca2+ 三磷酸腺苷酶（ATPase）积累Ca2+。诸如血管紧张素II等刺激会产生肌醇1,4,5 - 三磷酸（IP3），它调节SR的Ca2+通道。IP3结合会打开通道，并在细胞质中游离Ca2+（[Ca2+]i）浓度上产生一个“峰值”。这个峰值很大程度上是由于储存的Ca2+释放，因为在有无细胞外Ca2+的情况下，激素刺激都会产生类似的峰值。Ca2+从细胞排出，而不是由SR重新积累，负责使[Ca2+]i从刺激产生的峰值水平迅速下降。SR中Ca2+的释放和质膜Ca2+外流机制的激活会显著降低细胞内总Ca2+含量。质膜上有两种独立的Ca2+转运体，即Na(+)-Ca2+交换体和Ca2+ ATPase，它们积极地将Ca2+从SMC中排出。Na(+)-Ca2+交换体在很大程度上负责Ca2+排出的急性期，而质膜Ca2+ ATPase则有助于刺激后的SMC中Ca2+外流的持续增加。在Ca2+从SR释放并从细胞排出后，Ca2+通过通道进入，这维持了[Ca2+]i的适度增加以及SR的逐渐重新填充。线粒体在细胞内Ca2+信号传导中起重要作用。线粒体代谢对[Ca2+]i的短暂增加高度敏感，尽管线粒体不是Ca2+储存库。线粒体对Ca2+的摄取是由内膜上高度有利的电化学势差驱动的。线粒体通过H(+)-Ca2+或Na(+)-Ca2+交换体主动排出Ca2+。线粒体对Ca2+的摄取和排出有助于[Ca2+]i的时间和空间振荡。SR、细胞质、线粒体和细胞外环境之间加速的Ca2+循环是细胞受刺激的一个标志。
