两周模拟失重大鼠脑动脉平滑肌细胞Ca_L电流的变化

Changes in Ca_L channel currents of cerebrovascular smooth muscle cells isolated from 2-week simulated weightlessness rats

目的观察模拟失重2周后,大鼠脑动脉血管平滑肌细胞(vascular smooth muscle cells,VSMCs)L型电压依赖性钙离子通道(L-type voltage dependent calcium channel,CaL)功能的改变,以及钙通道激动剂BayK8644对通道电流的影响。方法以尾部悬吊大鼠模型模拟失重的影响。采用全细胞膜片钳记录模式,以Ba2+作为载流子,记录2周模拟失重后大鼠脑动脉VSMCs的CaL电流及钙通道激动剂Bay K 8644对其的影响,并测定相应的稳态激活与失活曲线及有关参数。结果与对照组相比,模拟失重2周后悬吊组大鼠已出现了典型的模拟失重效应,悬吊组大鼠脑动脉VSMCs的CaL的电流密度显著增加(P<0.05),且对钙通道激动剂Bay K 8644更敏感(P<0.05)。此外,与对照组相比,悬吊组大鼠脑动脉VSMCs的膜电容与接入电阻、CaL稳态失活曲线和稳态激活曲线等通道动力学特征无显著性改变。结论模拟失重2周可引起大鼠脑动脉平滑肌细胞CaL通道功能增强,这可能是模拟失重导致大鼠脑动脉血管收缩反应性增强的因素之一。

AIM To investigate the alterations of CaL in cerebral vascular smooth muscle cells isolated from rats subjected to a two-week simulated weightlessness and the influence of Bay K 8644 （an agonist of CaL） to the channel currents. METHODS Tail-suspended rat model was used to simulate the effects of microgravity. Whole-cell patch-clamp technique was used to record CaL currents before and after Bay K 8644 treatment, with intracellular Ca^2＋ concentration maintained at physiological level. The corresponding parameters such as steady state activation and inactivation curves were also recorded. RESULTS Whole-cell CaL current densities increased obviously and the sensitivity of CaL to Bay K 8644 also increased in cerebral vascular smooth muscle cells from suspension group. But membrane capacitance （Cm）, access resistance （Ra） and other parameters of CaL such as steady state activation/ inactivation curves, had no significant changes compared with those in control group. CONCLUSION These results suggest that enhanced CaL function of cerebrovascular smooth muscle cells induced by simulated microgravity may be one of the electrophysiological mechanisms that mediate the enhanced vasoreactivity of cerebrovascular smooth muscle cells during adaptation to simulated weightlessness in rats.