Ca2+ channels, Ca2+ sparks, and regulation of arterial smooth muscle function
Ca2+ channels, Ca2+ sparks, and regulation of arterial smooth muscle function
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DOI：
10.1007/s003920070095
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发表时间：
2000
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影响因子：
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通讯作者：
M. Gollasch;M. Löhn;M. Fürstenau;M. Nelson;Friedrich C Luft;Hermann Haller
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文献类型：
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作者：
M. Gollasch;M. Löhn;M. Fürstenau;M. Nelson;Friedrich C Luft;Hermann Haller
在心脏，骨骼肌和动脉肌肉，短暂的，空间局部升高[Ca 2 +]i，称为“Ca 2+火花”，已被观察到使用共聚焦激光扫描显微镜。Ca 2+火花被认为代表“基本”Ca 2+释放事件，其由肌浆网（SR）中的一个或多个ryanodine受体（RyR）通道产生。在横纹肌中，Ca 2+火花被认为是兴奋-收缩偶联的关键要素。在动脉平滑肌中，Ca 2+火花已被建议对抗肌源性血管收缩并影响血管舒张。使用发育模型，我们已经调查了是否RyRs引起的Ca 2+火花和激活的Ca 2+激活的K+（KCa）通道（STOCs）的功能作为“基本”的Ca 2+释放单位，调节动脉肌张力。整体[Ca ~（2+）] i增加可引起动脉平滑肌持续收缩，而Ca ~（2+）火花通过局部激活KCa通道引起血管舒张。在脑动脉中，整体[Ca ~（2+）] i和Ca ~（2+）火花频率< 10 ~（-2）Hz/细胞不能引起足够的KCa通道活性来调节平滑肌细胞的膜电位和肌源性张力。Ca 2+火花和STOCs的频率由调节蛋白激酶G和蛋白激酶A活性的试剂调节。我们的研究结果表明，“基本”钙释放单位可能代表新的，重要的治疗目标，调节功能的完整的动脉平滑肌组织。
In cardiac, skeletal, and arterial muscle, transient, spatially localized elevations in [Ca2+]i, termed “Ca2+sparks”, have been observed using confocal laser scanning microscopy. Ca2+sparks are thought to represent “elementary” Ca2+release events, which arise from one or more ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In striated muscle, Ca2+sparks are thought to be key elements of excitation-contraction coupling. In arterial smooth muscle, Ca2+sparks have been suggested to oppose myogenic vasoconstriction and to influence vasorelaxation. Using a developmental model, we have investigated whether RyRs causing Ca2+sparks and activation of Ca2+-activated K+(KCa) channels (STOCs) function as “elementary” Ca2+release units that regulate arterial mygenic tone. Whereas increases in theglobal[Ca2+]iinduce sustained constriction of arterial smooth muscle, Ca2+sparks induce vasodilation through thelocalactivation of KCachannels. In cerebral arteries, theglobalbulk [Ca2+]iand a Ca2+spark frequency < 10-2Hz/cell do not cause sufficient KCachannel activity to regulate membrane potential of smooth muscle cells and myogenic tone. The frequency of Ca2+sparks and STOCs is regulated by agents that modulate protein kinase G and protein kinase A activity. Our findings suggest that “elementary” Ca2+release units may represent novel, important therapeutic targets for regulating function of the intact arterial smooth muscle tissue.