The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels
The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K+ channels and activation of Ca2+-activated Cl- channels
复制标题
缓激肽在大鼠感觉神经元中诱导的急性伤害性信号是通过抑制 M 型 K 通道和激活 Ca2 激活的 Cl 通道介导的
DOI：
10.1172/jci41084
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发表时间：
2010-04-01
影响因子：
15.9
通讯作者：
Gamper, Nikita
中科院分区：
文献类型：
--
作者：
Liu, Boyi;Linley, John E.;Gamper, Nikita
缓激肽（BK）是一种炎症介质，也是最强的内源性疼痛诱导物质之一。当在组织损伤或炎症部位释放或外源性应用时，BK产生急性自发性疼痛并引起痛觉过敏（对潜在疼痛刺激的敏感性增加）。BK引起的自发性疼痛的机制知之甚少。在这里，我们报告说，在小的伤害性神经元从大鼠背根神经节，BK，通过其受体，PLC，并释放钙从细胞内存储，强烈抑制M型K+通道和开放钙激活的Cl-通道（CaCCs）编码的Tmem 16 a（也称为Ano 1）。这两种效应的总和解释了BK引起的DRG神经元去极化和AP放电增加。局部注射CaCC抑制剂和特异性M通道开放剂均能明显减弱BK的伤害性作用。这些结果为理解自发性炎症性疼痛提供了一个框架，并可能为治疗此类疼痛提供新的药物靶点。
Bradykinin (BK) is an inflammatory mediator and one of the most potent endogenous pain-inducing substances. When released at sites of tissue damage or inflammation, or applied exogenously, BK produces acute spontaneous pain and causes hyperalgesia (increased sensitivity to potentially painful stimuli). The mechanisms underlying spontaneous pain induced by BK are poorly understood. Here we report that in small nociceptive neurons from rat dorsal root ganglia, BK, acting through its By receptors, PLC, and release of calcium from intracellular stores, robustly inhibits M-type K+ channels and opens Ca2+-activated Cl- channels (CaCCs) encoded by Tmem16a (also known as Ano1). Summation of these two effects accounted for the depolarization and increase in AP firing induced by BK in DRG neurons. Local injection of inhibitors of CaCC and specific M-channel openers both strongly attenuated the nociceptive effect of local injections of BK in rats. These results provide a framework for understanding spontaneous inflammatory pain and may suggest new drug targets for treatment of such pain.