期刊
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
卷 35, 期 9, 页码 1127-1133出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1440-1681.2008.05018.x
关键词
calcium channels; calcium signals; Orai; stromal-interacting molecule (STIM); TRPC channels
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL055426] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL055426] Funding Source: Medline
1. Ca(2+) entry signals are crucial in the control of smooth muscle contraction. Smooth muscle cells are unusual in containing plasma membrane (PM) Ca(2+) entry channels that respond to voltage changes, receptor activation and Ca(2+) store depletion. 2. Activation of these channel subtypes is highly coordinated. The TRPC6 channel, widely expressed in most smooth muscle cell types, is largely non-selective to cations and is activated by diacylglycerol arising from receptor-induced phosholipase C activation. 3. Receptor activation results largely in Na(+) ion movement through TRPC6 channels, depolarization and subsequent activation of voltage-dependent L-type Ca(2+) channels. The TRPC6 channels also appear to be activated by mechanical stretch, resulting again in depolarization and L-type Ca(2+) channel activation. Such a coupling may be crucial in mediating the myogenic tone response in vascular smooth muscle. 4. The emptying of stores mediated by inositol 1,4,5-trisphosphate receptors triggers the endoplasmic reticulum (ER) Ca(2+) sensing protein stromal-interacting molecule (STIM) 1 to translocate into defined ER-PM junctional areas in which coupling occurs to Orai proteins, which serve as highly Ca(2+)-selective low-conductance Ca(2+) entry channels. 5. These ER-PM junctional domains may serve as crucial sites of interaction and integration between the function of store-operated, receptor-operated and voltage-operated Ca(2+) channels. The STIM, Orai and TRPC channels represent highly promising new pharmacological targets through which such control may be induced.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据