Voltage-gated ion channels in nociceptors: Modulation by cGMP
Voltage-gated ion channels in nociceptors: Modulation by cGMP
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DOI：
10.1152/jn.00355.2004
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发表时间：
2004-10-01
影响因子：
2.5
通讯作者：
Simon, SA
中科院分区：
文献类型：
--
作者：
Liu, L;Yang, T;Simon, SA
在组织或神经损伤中，释放促炎介质，其可以调节在伤害感受器中发现的多种离子通道。通道活性的变化主要通过细胞内通路的变化发生，可能导致痛觉过敏和异常性疼痛的病理状态。为了进一步了解通道活性变化的调控机制，我们使用大鼠三叉神经节神经元中辣椒素敏感的伤害性神经元的全细胞膜片钳记录来研究cGMP依赖性通路如何调节离子通道功能。加入8-（4-chlorophenylthio）-3 '，5'（CPT）-cGMP（一种离子通道的膜渗透性调节剂），可使诱发动作电位的数目减少36%，并分别抑制河豚毒素抗性（TTX-R）钠电流和I-A钾电流37%和32%。延迟整流钾（I-K）电流不受影响，这表明CPT-cGMP的影响是不可能产生的非特异性作用的通道活性作为一个结果的两亲性CPT-cGMP分子的吸附膜的双层组件。在CTP-cGMP存在下短杆菌肽A通道功能没有变化，这一结论得到了加强。总之，cGMP依赖性通路的激活部分通过降低电压门控TTX-R钠通道的活性来降低伤害感受器兴奋性。该途径可能是生产选择性镇痛药的目标。
In tissue or nerve injury, proinflammatory mediators are released that can modulate a variety of ion channels found in nociceptors. The changes in channel activity, which primarily occurs through changes in intracellular pathways, may lead to the pathological states of hyperalgesia and allodynia. To understand further the regulatory mechanisms underlying the changes in channel activity, we used whole cell patch-clamp recordings from capsaicin-sensitive nociceptive neurons in rat trigeminal ganglion neurons to examine how the cGMP-dependent pathways may regulate ion channel function. Addition of the 8-(4-chlorophenylthio)-3', 5' (CPT)-cGMP, a membrane permeant modulator of ion channels, decreased the number of evoked action potentials by 36% and inhibited the tetrodotoxin-resistant (TTX-R) sodium currents and I-A potassium currents by 37 and 32%, respectively. Delayed rectifier potassium (I-K) currents were unaffected, suggesting that the effects of CPT-cGMP are unlikely to arise from a nonspecific effect on channel activity as a consequence of the adsorption of amphipathic CPT-cGMP molecules to the membrane's bilayer component. This conclusion was reinforced by the lack of changes in gramicidin A channel function in the presence of CTP-cGMP. In summary, the activation of the cGMP-dependent pathways reduces nociceptor excitability, in part, by decreasing the activity of voltage-gated TTX-R sodium channels. This pathway may be a target for efforts to produce selective analgesics.