Differential regulation and recovery of intracellular Ca2+ in cerebral and small mesenteric arterial smooth muscle cells of simulated microgravity rat.

Differential regulation and recovery of intracellular Ca2+ in cerebral and small mesenteric arterial smooth muscle cells of simulated microgravity rat.
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模拟微重力大鼠脑和小肠系膜动脉平滑肌细胞内Ca2+的差异调节和恢复

DOI:
10.1371/journal.pone.0019775
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Xie MJ
Xie MJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xue JH;Chen LH;Zhao HZ;Pu YD;Feng HZ;Ma YG;Ma J;Chang YM;Zhang ZM;Xie MJ

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研究背景肠系膜血管和小动脉的差异性适应可能是航天后立位耐力不良的重要因素之一,但其细胞机制尚不清楚。我们推测,有一个差异调节细胞内钙离子的质膜CaL通道和ryanodine敏感的Ca 2+释放肌浆网(SR)在大脑和小肠系膜血管平滑肌细胞(VSMCs)的模拟微重力大鼠的功能的改变,分别确定。方法/主要发现Sprague-Dawley大鼠进行28天后肢减重模拟微重力。此外,尾部悬吊的大鼠在去除悬浮液后接受3或7天的恢复期。采用膜片钳和Western blotting方法检测CaL通道功能。通过激光共聚焦显微镜评估了咖啡因对ryanodine敏感的Ca 2+释放的作用。结果表明,模拟微重力可增加脑VSMCs CaL通道的功能和ryanodine敏感性Ca ~(2+)释放,而降低小肠系膜VSMCs CaL通道的功能和ryanodine敏感性Ca ~(2+)释放。此外,3或7天的恢复后,去除悬浮液可以恢复的CaL通道和ryanodine敏感的Ca 2+释放的功能,分别在大脑和小肠系膜VSMCs的控制水平。结论脑和小肠系膜VSMCs CaL通道和Ryanodine敏感性Ca 2+释放的差异性调节可能是导致脑血管系统自身调节改变和外周血管阻力不能充分提高的原因。
Background The differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca2+ determined by the alterations in the functions of plasma membrane CaL channels and ryanodine-sensitive Ca2+ releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively. Methodology/Principal Findings Sprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity. In addition, tail-suspended rats were submitted to a recovery period of 3 or 7 days after removal of suspension. The function of CaL channels was evaluated by patch clamp and Western blotting. The function of ryanodine-sensitive Ca2+ releases in response to caffeine were assessed by a laser confocal microscope. Our results indicated that simulated microgravity increased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral VSMCs, whereas, simulated microgravity decreased the functions of CaL channels and ryanodine-sensitive Ca2+ releases in small mesenteric VSMCs. In addition, 3- or 7-day recovery after removal of suspension could restore the functions of CaL channels and ryanodine-sensitive Ca2+ releases to their control levels in cerebral and small mesenteric VSMCs, respectively. Conclusions The differential regulation of CaL channels and ryanodine-sensitive Ca2+ releases in cerebral and small mesenteric VSMCs may be responsible for the differential regulation of intracellular Ca2+, which leads to the altered autoregulation of cerebral vasculature and the inability to adequately elevate peripheral vascular resistance in postspaceflight orthostatic intolerance.
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