Souslova V, Cesare P, Ding Y, Akopian A N, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenuis-Oosthuizen D, Smith A J, Kidd E J, Wood J N
Department of Biology, University College London, UK.
Nature. 2000 Oct 26;407(6807):1015-7. doi: 10.1038/35039526.
ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.
三磷酸腺苷（ATP）可激活损伤感受神经元（伤害感受器）并能引发疼痛感。ATP受体P2X3在伤害感受器中选择性表达，是七种ATP门控的阳离子选择性离子通道之一。在此我们证明，P2X3基因的缺失导致背根神经节神经元中快速脱敏的ATP门控阳离子电流丧失，并且结状神经节神经元对ATP的反应显示出因P2X(2/3)异源多聚体表达缺失而导致的动力学和药理学改变。无效突变体具有正常的感觉运动功能。对有害机械和热刺激的行为反应也正常，尽管福尔马林诱导的疼痛行为有所减少。相比之下，P2X3受体的缺失会导致慢性炎症中热痛觉过敏增强。值得注意的是，尽管背角神经元对机械和有害热刺激的反应正常，但P2X3基因敲除小鼠无法编码非有害“温热”刺激的强度。
