Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity
Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity
复制标题
模拟微重力过程中大鼠大脑和后肢动脉钾通道的差异激活
DOI：
10.1152/ajpheart.00143.2004
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Ma, J
中科院分区：
文献类型：
--
作者：
Fu, ZJ;Xie, MJ;Ma, J
本研究的目的是测试这一假设，即在模拟微重力条件下，大脑和后肢动脉的差异自动调节是由不同解剖区域动脉血管平滑肌细胞（VSMCs）中K+通道的差异激活介导或调节的。对Sprague-Dawley大鼠进行了1周和4周的尾部悬吊，以模拟由于短期和中期微重力引起的心血管失调效应。用药理学方法和膜片钳技术研究了VSMCs的K+通道功能。大电导Ca 2+激活的K+（BKCa）和电压门控K+（K-v）电流通过分别从之前的电流减去应用1 mM四乙基铵（TEA）和1 mM TEA + 3 mM 4-氨基吡啶（4-AP）后记录的电流来确定。对于脑血管，1周和4周模拟微重力后，分别显著降低了基底动脉环对TEA（一种BKCa阻滞剂）和4-AP（一种Kv阻滞剂）的正常收缩力。与对照组相比，悬吊大鼠大脑中动脉VSMCs的去极化膜电位（E-m）明显增高，K+电流密度明显降低。此外，降低总电流密度是由于更小的BKCa和更小的K-v电流密度在大脑VSMCs后1和4周尾部悬吊，分别。对于后腿血管，从1周和4周悬浮大鼠的第二至第六阶小肠系膜动脉分离的VSMC的总电流、BKCa电流和K-v电流的E-m更负，K+电流密度更大。这些结果表明，在短期和中期模拟微重力下，大脑和后躯VSMCs的K+通道发生差异激活。这进一步表明，不同的配置文件的通道重塑可能发生在VSMCs作为一个重要的潜在的细胞机制，以介导和调节微重力条件下的差异血管适应。
The purpose of this study was to test the hypothesis that differential autoregulation of cerebral and hindquarter arteries during simulated microgravity is mediated or modulated by differential activation of K+ channels in vascular smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague-Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the cardiovascular deconditioning effect due to short- and medium-term microgravity. K+ channel function of VSMCs was studied by pharmacological methods and patch-clamp techniques. Large-conductance Ca2+-activated K+ (BKCa) and voltage-gated K+ (K-v) currents were determined by subtracting the current recorded after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4-aminopyridine (4-AP), respectively, from that of before. For cerebral vessels, the normalized contractility of basilar arterial rings to TEA, a BKCa blocker, and 4-AP, a Kv blocker, was significantly decreased after 1-and 4-wk simulated microgravity, respectively. VSMCs isolated from the middle cerebral artery branches of suspended rats had a more depolarized membrane potential (E-m) and a smaller K+ current density compared with those of control rats. Furthermore, the reduced total current density was due to smaller BKCa and smaller K-v current density in cerebral VSMCs after 1- and 4-wk tail suspension, respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative E-m and larger K+ current densities for total, BKCa, and K-v currents. These results indicate that differential activation of K+ channels occur in cerebral and hindquarter VSMCs during short- and medium-term simulated microgravity. It is further suggested that different profiles of channel remodeling might occur in VSMCs as one of the important underlying cellular mechanisms to mediate and modulate differential vascular adaptation during microgravity.