Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig
Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig
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DOI：
10.1113/jphysiol.2002.022848
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发表时间：
2002-09-01
影响因子：
5.5
通讯作者：
Undem, BJ
中科院分区：
文献类型：
--
作者：
Kollarik, M;Undem, BJ
在豚鼠离体气道神经标本上，研究了呼吸道传入神经对低pH反应的机制。细胞外记录来自单个颈静脉或结节迷走神经节神经元，这些神经元将其感觉纤维投射到呼吸道。将含有机械敏感感受野的呼吸道组织暴露在酸性溶液中。在感受野快速而短暂地(类似于S 3)注射1 mM柠檬酸，可持续地在伤害性C纤维(41/44)和结状A-三角洲纤维(29/30)上诱发动作电位放电，这些纤维正在迅速适应低阈值机械传感器(RAR样纤维)。相比之下，柠檬酸只激活了8/17高阈值机械敏感型颈静脉ADelta纤维。RAR样纤维对酸性溶液的敏感性略高于C纤维(pH阈值6.7)。对类似S酸处理的RAR样纤维的反应不受香草酸受体1拮抗剂卡萨西平(10微米)的影响，并且迅速失活(动作电位放电在给酸结束前终止)。PH的逐渐降低并不能激活RAR样纤维，即使在pH降到接近5.0时也是如此。C纤维对pH逐渐降低的反应是持续动作电位放电，这种反应可被卡萨西平(10um)几乎消除，并被另一种VR1拮抗剂Ido-resiniferatoxin(1um)抑制70%以上。相反，血管紧张素转换酶受体拮抗剂不影响S对pH类似5.0的短暂性刺激的C纤维反应。我们认为，低pH激活豚鼠呼吸道传入是通过缓慢失活和快速失活两种机制来实现的。我们推测，这种缓慢失活的机制存在于C纤维中，而不存在于RAR样纤维中，是由VR1介导的。这种快速失活机制独立于VR1发挥作用，具有类似于酸敏感离子通道(ASIC)的特征，并在C纤维和RAR样纤维的呼吸道末端都发现。
The mechanisms underlying the response of airway afferent nerves to low pH were investigated in an isolated guinea-pig airway nerve preparation. Extracellular recordings were made from single jugular or nodose vagal ganglion neurons that projected their sensory fibers into the airways. The airway tissue containing the mechanically sensitive receptive fields was exposed into acidic solutions. Rapid and transient (similar to3 s) administration of 1 mm citric acid to the receptive field consistently induced action potential discharge in nociceptive C-fibers (41/44) and nodose Adelta fibres (29/30) that are rapidly adapting low threshold mechanosensors (RAR-like fibres). In contrast, citric acid activated only 8/17 high threshold mechanosensitive jugular Adelta fibres. The RAR-like fibres were slightly more sensitive than C-fibres to acidic solutions (pH threshold > 6.7). The RAR-like fibres response to the similar to3 s acid treatment was not affected by a vanilloid receptor 1 (VR1) antagonist, capsazepine (10 mum), and was rapidly inactivating (action potential discharge terminated before the acid administration was completed). Gradual reduction of pH did not activate the RAR-like fibres even when the pH was reduced to similar to5.0. The C-fibres responded to the gradual reduction of pH with persistent action potential discharge that was nearly abolished by capsazepine (10 mum) and inhibited by over 70 % with another VR1 antagonist iodo-resiniferatoxin (1 mum). In contrast the C-fibre response to the transient similar to3 s exposure to pH similar to5.0 was not affected by the VR1 antagonists. We conclude that activation of guinea-pig airway afferents by low pH is mediated by both slowly and rapidly inactivating mechanisms. We hypothesize that the slowly inactivating mechanism, present in C-fibres but not in RAR-like fibres, is mediated by VR1. The rapidly inactivating mechanism acts independently of VR1, has characteristics similar to acid sensing ion channels (ASICs) and is found in the airway terminals of both C-fibres and RAR-like fibres.