Kotlikoff M I, Wang Y X
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 3):S109-14. doi: 10.1164/ajrccm.158.supplement_2.13tac600.
Rapid progress has been made in the determination of specific ion channels expressed in airway smooth muscle cells and their role in excitation-contraction coupling. The combination of molecular biology and molecular physiology has provided insight into the properties of voltage-dependent cation (calcium and potassium) channels and their regulation by excitatory and inhibitory signaling processes. In this brief review, we will focus on calcium release and calcium-activated chloride channels. The former channels mediate receptor-activated calcium release, and the latter channels are opened following this release event. Moreover, the discovery of spontaneous calcium release events, or "calcium sparks," in smooth muscle, suggests an unanticipated level of regulation. Intracellular calcium release can drive electrical activity by the activation of calcium-dependent sarcolemmal ion channels, including calcium-activated chloride channels. These channels activate briefly but undergo a rapid phosphorylation by calcium/calmodulin-dependent protein kinase, which uncouples channel activity from cytosolic calcium. The coupling between intracellular calcium release and depolarizing chloride currents represents a potentially important signaling system in airway smooth muscle.
在气道平滑肌细胞中表达的特定离子通道的确定及其在兴奋-收缩偶联中的作用方面已经取得了迅速进展。分子生物学和分子生理学的结合为电压依赖性阳离子(钙和钾)通道的特性及其受兴奋性和抑制性信号传导过程的调节提供了深入了解。在这篇简短的综述中,我们将重点关注钙释放通道和钙激活氯通道。前者介导受体激活的钙释放,后者在该释放事件后开放。此外,在平滑肌中发现自发钙释放事件,即“钙火花”,提示了一种意想不到的调节水平。细胞内钙释放可通过激活钙依赖性肌膜离子通道(包括钙激活氯通道)来驱动电活动。这些通道短暂激活,但会被钙/钙调蛋白依赖性蛋白激酶迅速磷酸化,从而使通道活性与胞质钙解偶联。细胞内钙释放与去极化氯电流之间的偶联代表了气道平滑肌中一个潜在的重要信号系统。