GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones
GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones
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DOI：
10.1113/jphysiol.2003.039131
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发表时间：
2003-04-15
影响因子：
5.5
通讯作者：
Wood, JN
中科院分区：
文献类型：
--
作者：
Baker, MD;Chandra, SY;Wood, JN
外周疼痛阈值受炎症介质的作用所调节。一些炎症介质通过电压门控钠通道上的G蛋白偶联受体发挥作用。我们发现，一种低阈值、对河豚毒素有抗性的持续性钠电流（归因于Na(V)1.9）可被GTP及其不可水解的类似物GTP -γ - S上调，但不被GDP上调。在细胞内液中加入GTP -γ - S（500 μM）可使最大电流幅度在5分钟内增加>300%。在电流钳模式下，从 -90 mV的静息电位评估，持续性电流的上调与动作电位诱发阈值更负（降低15 - 16 mV）相关。在没有低阈值电流的神经元中或使用细胞内GDP时未观察到这种现象（P < 0.001）。此外，持续性电流上调使神经元去极化。在 -60 mV时，只有当持续性电流上调时，细胞内GTP -γ - S才会使原本静息的神经元产生自发活动。这些发现表明，持续性电流的调节对伤害感受器的兴奋性具有重要影响。
Peripheral pain thresholds are regulated by the actions of inflammatory mediators. Some act through G-protein-coupled receptors on voltage-gated sodium channels. We have found that a low-threshold, persistent tetrodotoxin-resistant Na(+) current, attributed to Na(V)1.9, is upregulated by GTP and its non-hydrolysable analogue GTP-gamma-S, but not by GDP. Inclusion of GTP-gamma-S (500 mum) in the internal solution led to an increase in maximal current amplitude of > 300% within 5 min. In current damp, upregulation of persistent current was associated with a more negative threshold for action potential induction (by 15-16 mV) assessed from a holding potential of -90 mV. This was not seen in neurones without the low-threshold current or with internal GDP (P < 0.001). In addition, persistent current upregulation depolarized neurones. At -60 mV, internal GTP-gamma-S led to the generation of spontaneous activity in initially silent neurones only when persistent current was upregulated. These findings suggest that regulation of the persistent current has important consequences for nociceptor excitability.