Xie Man-Jiang, Zhang Li-Fan, Ma Jin, Cheng Hong-Wei
Department of Aerospace Physiology, Fourth Military Medical University, Xi'an 710032, China.
Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1265-76. doi: 10.1152/ajpheart.00074.2005. Epub 2005 May 13.
Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca(2+)-activated K(+) (BK(Ca)), voltage-gated K(+) (K(V)), and L-type voltage-dependent Ca(2+) (Ca(L)) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, K(V), BK(Ca), and Ca(L) currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. K(V) current density decreased in Sus rats vs. Con rats [1.07 +/- 0.14 (n = 22) vs. 1.31 +/- 0.28 (n = 16) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 1.70 +/- 0.37 (n = 23) vs. 0.88 +/- 0.22 (n = 19) pA/pF at +20 mV (P < 0.05); Ca(L): -2.17 +/- 0.21 (n = 35) vs. -1.31 +/- 0.10 (n = 26) pA/pF at +10 mV (P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: K(V) current density decreased [1.03 +/- 0.33 (n = 9) vs. 1.62 +/- 0.64 (n = 9) pA/pF at +20 mV (P < 0.05)] and BK(Ca) and Ca(L) current densities increased [BK(Ca): 2.54 +/- 0.47 (n = 11) vs. 1.12 +/- 0.33 (n = 12) pA/pF at +20 mV (P < 0.05); Ca(L): -3.99 +/- 0.53 (n = 12) vs. -2.28 +/- 0.20 (n = 10) pA/pF at +20 mV (P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.
由于静水压力梯度的消除，暴露于微重力环境会导致整个脑血管系统的跨壁压力持续升高。我们推测，脑血管平滑肌细胞（VSMC）中可能会发生类似于高血压相关的离子通道重塑，并在微重力期间脑血管的向上自动调节中发挥作用。将Sprague-Dawley大鼠进行4周的尾部悬吊（Sus）以模拟微重力对心血管的影响。采用全细胞电压钳技术研究了Sus大鼠和对照（Con）大鼠脑VSMC的大电导钙激活钾（BK(Ca)）、电压门控钾（K(V)）和L型电压依赖性钙（Ca(L)）电流。在相同实验条件下，还研究了成年自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）脑VSMC的K(V)、BK(Ca)和Ca(L)电流。与Con大鼠相比，Sus大鼠的K(V)电流密度降低[在+20 mV时为1.07±0.14（n = 22）对1.31±0.28（n = 16）pA/pF，P < 0.05]，而BK(Ca)和Ca(L)电流密度增加[BK(Ca)：在+20 mV时为1.70±0.37（n = 23）对0.88±0.22（n = 19）pA/pF，P < 0.05；Ca(L)：在+10 mV时为-2.17±0.21（n = 35）对-1.31±0.10（n = 26）pA/pF，P < 0.05]。在SHR与WKY脑VSMC中也观察到了类似变化：K(V)电流密度降低[在+20 mV时为1.03±o.33（n = 9）对1.62±0.64（n = 9）pA/pF，P < 0.05]，BK(Ca)和Ca(L)电流密度增加[BK(Ca)：在+20 mV时为2.54±0.47（n = 11）对1.12±0.33（n = 12）pA/pF，P < 0.05；Ca(L)：在+20 mV时为-3.99±0.53（n = 12）对-2.28±0.20（n = 10）pA/pF，P < 0.05]。这些发现支持了我们的假设，并讨论了它们对空间心血管研究的影响。
