Differential activation of ion channels by inositol 1,4,5-trisphosphate (IP3)- and ryanodine-sensitive calcium stores in rat basilar artery vasomotion
Differential activation of ion channels by inositol 1,4,5-trisphosphate (IP3)- and ryanodine-sensitive calcium stores in rat basilar artery vasomotion
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DOI：
10.1113/jphysiol.2002.027904
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发表时间：
2002-12-01
影响因子：
5.5
通讯作者：
Hill, CE
中科院分区：
文献类型：
--
作者：
Haddock, RE;Hill, CE
在正常生理和病理生理条件下，脑血管都可以记录到自发的、有节律的收缩或血管运动。利用电生理学研究膜电位的变化，比率钙指示剂Fura-2 AM研究动脉壁和单个平滑肌细胞（SMC）中[Ca 2 +]（i）的变化，以及视频显微镜研究血管直径的变化，我们研究了幼年大鼠基底动脉血管舒缩的细胞机制。在血管舒缩过程中，膜电位和[Ca ~（2+）]（i）的节律性振荡先于节律性收缩。硝苯地平使平滑肌细胞去极化，消除节律性收缩和去极化。[Ca2动脉壁[Ca ~（2+）] i振荡减少且不规则，而相邻SMC [Ca ~（2+）] i振荡不再同步。BAPTA-AM、thapsigargin和U 73122使SMC超极化，舒张血管，降低基础钙水平并消除血管舒缩。氯化物替代废除节律活动，去极化SMC，增加基础钙水平和收缩血管，而尼氟灭酸和DIDS废除血管舒缩。Ryanodine、Charybdotoxin和TRAM-34，而不是伊比利亚毒素、4-氨基吡啶或apamin，均使SMC去极化，并增加节律性去极化和[Ca 2 +]（i）振荡的频率。我们的结论是，血管舒缩在基底动脉依赖于从IP 3（肌醇1，4，5，-三磷酸）-敏感的商店激活钙依赖性氯离子通道，以去甲平滑肌细胞的细胞内钙的释放。去极化反过来激活电压依赖性钙通道，通过细胞外钙的流入使相邻细胞的收缩同步。随后钙诱导的钙释放从ryanodine敏感的商店激活中间电导钾通道，超极化的SMC和收缩周期的再生提供了一个负反馈途径。
Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. Using electrophysiology to study changes in membrane potential, the ratiometric calcium indicator Fura-2 AM to study changes in [Ca2+](i) in both the arterial wall and in individual smooth muscle cells (SMCs), and video microscopy to study changes in vessel diameter, we have investigated the cellular mechanisms underlying vasomotion in the juvenile rat basilar artery. During vasomotion, rhythmical oscillations in both membrane potential and [Ca2+](i) were found to precede rhythmical contractions. Nifedipine depolarized SMCs and abolished rhythmical contractions and depolarizations. [Ca2+] i oscillations in the arterial wall became reduced and irregular, while [Ca2+](i) oscillations in adjacent SMCs were no longer synchronized. BAPTA-AM, thapsigargin and U73122 hyperpolarized SMCs, relaxed the vessel, decreased basal calcium levels and abolished vasomotion. Chloride substitution abolished rhythmical activity, depolarized SMCs, increased basal calcium levels and constricted the vessel, while niflumic acid and DIDS abolished vasomotion. Ryanodine, charybdotoxin and TRAM-34, but not iberiotoxin, 4-aminopyridine or apamin, each depolarized SMCs and increased the frequency of rhythmical depolarizations and [Ca2+](i) oscillations. We conclude that vasomotion in the basilar artery depends on the release of intracellular calcium from IP3 (inositol 1,4,5,-trisphosphate) -sensitive stores which activates calcium-dependent chloride channels to depolarize SMCs. Depolarization in turn activates voltage-dependent calcium channels, synchronizing contractions of adjacent cells through influx of extracellular calcium. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates an intermediate conductance potassium channel, hyperpolarizing the SMCs and providing a negative feedback pathway for regeneration of the contractile cycle.