Leblanc Normand, Ledoux Jonathan, Saleh Sohag, Sanguinetti Amy, Angermann Jeff, O'Driscoll Kate, Britton Fiona, Perrino Brian A, Greenwood Iain A
Department of Pharmacology, Centre of Biomedical Research Excellence (COBRE), University of Nevada School of Medicine, Reno, NV, USA.
Can J Physiol Pharmacol. 2005 Jul;83(7):541-56. doi: 10.1139/y05-040.
Calcium-activated chloride channels (ClCa) are ligand-gated anion channels as they have been shown to be activated by a rise in intracellular Ca2+ concentration in various cell types including cardiac, skeletal and vascular smooth muscle cells, endothelial and epithelial cells, as well as neurons. Because ClCa channels are normally closed at resting, free intracellular Ca2+ concentration (approximately 100 nmol/L) in most cell types, they have generally been considered excitatory in nature, providing a triggering mechanism during signal transduction for membrane excitability, osmotic balance, transepithelial chloride movements, or fluid secretion. Unfortunately, the genes responsible for encoding this class of ion channels is still unknown. This review centers primarily on recent findings on the properties of these channels in smooth muscle cells. The first section discusses the functional significance and biophysical and pharmacological properties of ClCa channels in smooth muscle cells, and ends with a description of 2 candidate gene families (i.e., CLCA and Bestrophin) that are postulated to encode for these channels in various cell types. The second section provides a summary of recent findings demonstrating the regulation of native ClCa channels in vascular smooth muscle cells by calmodulin-dependent protein kinase II and calcineurin and how their fine tuning by these enzymes may influence vascular tone.
钙激活氯离子通道（ClCa）是配体门控阴离子通道，因为在包括心肌、骨骼肌和血管平滑肌细胞、内皮细胞和上皮细胞以及神经元在内的各种细胞类型中，它们已被证明可被细胞内Ca2+浓度升高激活。由于在大多数细胞类型中，ClCa通道在静息时通常是关闭的，细胞内游离Ca2+浓度（约100 nmol/L），因此它们通常被认为本质上是兴奋性的，在信号转导过程中为膜兴奋性、渗透平衡、跨上皮氯离子移动或液体分泌提供触发机制。不幸的是，负责编码这类离子通道的基因仍然未知。本综述主要围绕平滑肌细胞中这些通道特性的最新发现展开。第一部分讨论了平滑肌细胞中ClCa通道的功能意义、生物物理和药理学特性，并以描述2个候选基因家族（即CLCA和Bestrophin）作为结尾，这2个家族被推测在各种细胞类型中编码这些通道。第二部分总结了最近的研究结果，这些结果表明钙调蛋白依赖性蛋白激酶II和钙调神经磷酸酶对血管平滑肌细胞中天然ClCa通道的调节作用，以及这些酶对它们的微调如何影响血管张力。
