Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone
Reduced Ca2+ spark activity after subarachnoid hemorrhage disables BK channel control of cerebral artery tone
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DOI：
10.1038/jcbfm.2010.143
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发表时间：
2011-01-01
影响因子：
6.3
通讯作者：
Wellman, George C.
中科院分区：
文献类型：
--
作者：
Koide, Masayo;Nystoriak, Matthew A.;Wellman, George C.
细胞内Ca2+释放事件（“Ca2+火花”）和大电导Ca2+激活钾（BK）通道的瞬时激活代表了脑血管系统中重要的血管扩张途径。考虑到蛛网膜下腔出血（SAH）后经常发生脑动脉收缩，我们的目的是确定SAH模型兔脑动脉肌细胞中Ca2+火花和BK通道活性是否降低。使用激光扫描共聚焦显微镜，我们观察到Ca2+火花活性降低了50%，反映了功能Ca2+火花放电位点数量的减少。膜片钳电生理学显示Ca2+火花诱导的瞬态BK电流也有类似的减少，但BK通道密度和单通道特性没有变化。与活性Ca2+火花位点的减少一致，定量实时PCR和western blotting显示，在SAH动物的脑动脉中，ryanodine受体2型（RyR-2）的表达减少，RyR-2稳定蛋白FKBP12.6的表达增加。此外，Ca2+火花（ryanodine）或BK通道（paxilline）抑制剂在对照动物中收缩动脉，但在SAH动物中没有。这项研究表明，sah诱导的亚细胞Ca2+信号事件减少，使BK通道活性丧失，导致脑动脉收缩。这种现象可能导致动脉瘤性SAH后脑血流量减少和预后不良。脑血流与代谢杂志（2011）31,3 -16；doi: 10.1038 / jcbfm.2010.143;2010年8月25日在线发布
Intracellular Ca2+ release events ('Ca2+ sparks') and transient activation of large-conductance Ca2+-activated potassium (BK) channels represent an important vasodilator pathway in the cerebral vasculature. Considering the frequent occurrence of cerebral artery constriction after subarachnoid hemorrhage (SAH), our objective was to determine whether Ca2+ spark and BK channel activity were reduced in cerebral artery myocytes from SAH model rabbits. Using laser scanning confocal microscopy, we observed similar to 50% reduction in Ca2+ spark activity, reflecting a decrease in the number of functional Ca2+ spark discharge sites. Patch-clamp electrophysiology showed a similar reduction in Ca2+ spark-induced transient BK currents, without change in BK channel density or single-channel properties. Consistent with a reduction in active Ca2+ spark sites, quantitative real-time PCR and western blotting revealed decreased expression of ryanodine receptor type 2 (RyR-2) and increased expression of the RyR-2-stabilizing protein, FKBP12.6, in the cerebral arteries from SAH animals. Furthermore, inhibitors of Ca2+ sparks (ryanodine) or BK channels (paxilline) constricted arteries from control, but not from SAH animals. This study shows that SAH-induced decreased subcellular Ca2+ signaling events disable BK channel activity, leading to cerebral artery constriction. This phenomenon may contribute to decreased cerebral blood flow and poor outcome after aneurysmal SAH. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 3-16; doi:10.1038/jcbfm.2010.143; published online 25 August 2010