星形胶质细胞游离Ca2+浓度的直接偏差控制多小动脉张力状态

J. Haidey, G. Gordon
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引用次数: 1

摘要

星形胶质细胞通过血管收缩和血管舒张途径对急性分离的脑切片中的微血管直径进行双向控制,这些途径可以通过端足中的游离Ca2+浓度和/或组织的代谢状态来不同地募集。然而,Ca2+水平假说尚未通过直接操作进行验证。为了克服这一问题,我们使用Ca2+钳全细胞修补小动脉周围星形胶质细胞,将星形胶质细胞游离Ca2+改变为不同浓度,并检测血管反应。我们发现,在预收缩的小动脉中,将Ca2+夹持在近似静止值(100nM)对小动脉直径没有影响。然而,适度升高至250nM引起持续的血管舒张,其被COX-1拮抗剂SC-560(500nM)阻断。血管舒张至250 nM Ca2+对代谢状态敏感,因为当氧张力显著升高时,它转化为血管收缩。在正常氧气中,将星形胶质细胞Ca2+钳制在远高于静息水平(750 nM)的水平会产生持续的血管收缩,在20-HETE阻断剂HET0016(1μM)中转化为血管舒张。通过添加SC-560(500nM)完全阻断了这种反应,表明20 HETE诱导的血管收缩主导了COX-1的扩张作用。这些数据表明,星形胶质细胞游离Ca2+的直接变化可以通过不同的介质控制多种小动脉张力状态。
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Direct Deviations in Astrocyte Free Ca2+ Concentration Control Multiple Arteriole Tone States
Astrocytes elicit bidirectional control of microvascular diameter in acutely isolated brain slices through vasoconstriction and vasodilation pathways that can be differentially recruited via the free Ca2+ concentration in endfeet and/or the metabolic status of the tissue. However, the Ca2+-level hypothesis has not been tested using direct manipulation. To overcome this, we used Ca2+-clamp whole-cell patching of peri-arteriole astrocytes to change astrocyte-free Ca2+ to different concentrations and examined the vascular response. We discovered that clamping Ca2+ at the approximate resting value (100 nM) had no impact on arteriole diameter in a pre-constricted arteriole. However, a moderate elevation to 250 nM elicited sustained vasodilation that was blocked by the COX-1 antagonist SC-560 (500 nM). The vasodilation to 250 nM Ca2+ was sensitive to the metabolic state, as it converted to vasoconstriction when oxygen tension was dramatically elevated. In normal oxygen, clamping astrocyte Ca2+ well above the resting level (750 nM) produced sustained vasoconstriction, which converted to vasodilation in the 20-HETE blocker HET0016 (1 μM). This response was fully blocked by the addition of SC-560 (500 nM), showing that 20-HETE-induced vasoconstriction dominated the dilatory action of COX-1. These data demonstrate that direct changes in astrocyte free Ca2+ can control multiple arteriole tone states through different mediators.
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