Peng H, Matchkov V, Ivarsen A, Aalkjaer C, Nilsson H
Department of Physiology and Danish Biomembrane Research Centre, Aarhus University, Aarhus, Denmark.
Circ Res. 2001 Apr 27;88(8):810-5. doi: 10.1161/hh0801.089603.
Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of vasomotion. We suggest that intermittent release of Ca(2+) from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca(2+) release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal Ca(2+) imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca(2+) in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of Ca(2+) after some time, and vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca(2+) release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca(2+) release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate vasomotion in an unsynchronized artery as expected from the model.
血管运动是动脉张力的规律性变化。在我们的研究中，我们提出了一个血管运动起始的模型。我们认为，肌浆网（SR，胞质振荡器）中Ca(2+)的间歇性释放，最初在血管平滑肌细胞之间是不同步的，后来变得同步从而引发血管运动。这种同步是通过细胞膜上的离子电流实现的，该电流由振荡的Ca(2+)释放激活。这种电流导致膜电位振荡，使血管壁中的SR同步并启动血管运动。因此，血管壁的起搏器可以设想为一组分散的单个胞质振荡器，它们通过与细胞膜的相互作用而被带动同步。该模型得到了实验数据的支持。共聚焦Ca(2+)成像以及分离的大鼠阻力动脉中的等长力发展表明，低浓度去甲肾上腺素会在血管平滑肌中诱导SR依赖性的不同步Ca(2+)波。在内皮存在的情况下，一段时间后这些波会转变为Ca(2+)的整体同步振荡，并出现血管运动。如果向浴液中添加8-溴-cGMP，在没有内皮的情况下也能看到同步现象。使用膜片钳技术和微电极，我们表明Ca(2+)释放可以激活来自动脉的分离平滑肌细胞中的内向电流并导致去极化。Ca(2+)释放的这些电生理效应是cGMP依赖性的，这与它们对cGMP依赖性同步很重要的可能性是一致的。对该模型的进一步支持是这样的观察结果：如模型所预期的，一个短暂的电流脉冲可以在未同步的动脉中引发血管运动。
