Zang W J, Balke C W, Wier W G
Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore St. Baltimore, MD 21201, USA.
Cell Calcium. 2001 May;29(5):327-34. doi: 10.1054/ceca.2000.0193.
Confocal laser scanning microscopy and Fluo-4 were used to visualize Ca(2+) transients within individual smooth muscle cells (SMC) of rat resistance arteries during alpha(1)-adrenoceptor activation. The typical spatio-temporal pattern of [Ca(2+)] in an artery after exposure to a maximally effective concentration of phenylephrine (PE, 10.0 microM) was a large, brief, relatively homogeneous Ca(2+) transient, followed by Ca(2+) waves, which then declined in frequency over the course of 5 min and which were asynchronous in different SMC. Concentration-Effect (CE) curves relating the concentration of PE (range: 0.1 microM to 10.0 microM) to the effects (fraction of cells producing at least one Ca(2+) wave, and number of Ca(2+) waves during 5 min) had EC(50) values of approximately 0.5 microM and approximately 1.0 microM respectively. The initial Ca(2+) transient and the subsequent Ca(2+) waves were abolished in the presence of caffeine (10.0 mM). A repeated exposure to PE, 1.5 min after the first had ended, elicited fewer Ca(2+) waves in fewer cells than did the initial exposure. Caffeine-sensitive Ca(2+) stores were not depleted at this time, however, as caffeine alone was capable of inducing a large release of Ca(2+)1.5 min after PE. In summary, the mechanism of a graded response to graded alpha(1)-adrenoceptor activation is the progressive 'recruitment' of individual SMC, which then respond in 'all or none' fashion (viz. asynchronous Ca(2+) waves). Ca(2+) signaling continues in the arterial wall throughout the time-course (at least 5 min) of activation of alpha(1)-adrenoceptors. The fact that the Ca(2+) waves are asynchronous accounts for the previously reported fall in 'arterial wall [Ca(2+)]' (i.e. spatial average [Ca(2+)] over all cells).
采用共聚焦激光扫描显微镜和Fluo-4来观察大鼠阻力动脉单个平滑肌细胞（SMC）在α1-肾上腺素能受体激活过程中的Ca(2+)瞬变。在暴露于最大有效浓度的去氧肾上腺素（PE，10.0 μM）后，动脉中[Ca(2+)]的典型时空模式是一个大的、短暂的、相对均匀的Ca(2+)瞬变，随后是Ca(2+)波，其频率在5分钟内逐渐下降，且在不同的SMC中是异步的。将PE浓度（范围：0.1 μM至10.0 μM）与效应（产生至少一个Ca(2+)波的细胞比例以及5分钟内Ca(2+)波的数量）相关的浓度-效应（CE）曲线的EC(50)值分别约为0.5 μM和约1.0 μM。在存在咖啡因（10.0 mM）的情况下，最初的Ca(2+)瞬变和随后的Ca(2+)波被消除。在第一次暴露结束1.5分钟后重复暴露于PE，与最初暴露相比，在更少的细胞中引发的Ca(2+)波更少。然而，此时咖啡因敏感的Ca(2+)储存并未耗尽，因为单独的咖啡因在PE后1.5分钟能够诱导大量的Ca(2+)释放。总之，对分级α1-肾上腺素能受体激活的分级反应机制是单个SMC的逐步“募集”，然后以“全或无”方式做出反应（即异步Ca(2+)波）。在α1-肾上腺素能受体激活的整个时间过程（至少5分钟）中，Ca(2+)信号在动脉壁中持续存在。Ca(2+)波是异步的这一事实解释了先前报道的“动脉壁[Ca(2+)]”下降（即所有细胞上的空间平均[Ca(2+)]）。
