Modulation of IA currents by capsaicin in rat trigerninal ganglion neurons
Modulation of IA currents by capsaicin in rat trigerninal ganglion neurons
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DOI：
10.1152/jn.00210.2002
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发表时间：
2003-03-01
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;Simon, SA
当辣椒素（辣椒中的刺激性化合物）作用于上皮细胞时，会产生疼痛、异常性疼痛和痛觉过敏。我们使用全细胞路径钳研究了辣椒素诱导的某些反应是否可能是辣椒素阻断 I-A 电流的结果，I-A 电流的减少（例如在损伤时发生）会增加神经元兴奋性。在辣椒素敏感 (CS) 大鼠三叉神经节 (TG) 神经元中，辣椒素以剂量依赖性方式抑制 I-A 电流。 1 μM 辣椒素使 I-A 电流降低 49%。在辣椒素不敏感 (CIS) 大鼠 TG 神经元或小直径小鼠 VR1 -/- 神经元中，1 μM 辣椒素分别抑制 I-A 电流 9% 和 3%。这些数据表明，在 CS 神经元中，绝大多数辣椒素诱导的 I-A 电流抑制是香草酸受体激活的结果。辣椒素 (1 μM) 不会改变 I-A 电导-电压关系，但将失活电压曲线移动约 15 mV 至超极化电压，从而增加静息电位下失活 I-A 通道的数量。 I-A 电流相对不受 1 mM CTP-cAMP 或 500 nM 佛波醇-12, 13-二丁酯（一种蛋白激酶 C 激动剂）的影响，但受到 1 mM CTP-cGMP 或 25 muM N-(6-氨基己基)-5-氯-1-萘磺酰胺 HCl（一种钙钙调蛋白激酶抑制剂）的抑制 20-30%。在 0.5 μM KT5823（一种蛋白激酶 G (PKG) 通路抑制剂）存在的情况下，1 μM 辣椒素仅抑制 I-A 26%。总之，在 CS 神经元中，辣椒素通过激活香草酸受体来降低 I-A 电流。这种激活（部分通过 cGMP-PKG 和钙调蛋白依赖性途径的激活）应导致辣椒素敏感伤害感受器的兴奋性增加。
When capsaicin, the pungent compound in hot pepper, is applied to epithelia it produces pain, allodynia, and hyperalgesia. We investigated, using whole cell path clamp, whether some of these responses induced by capsaicin could be a consequence of capsaicin blocking I-A currents, a reduction in which, such as occurs in injury, increases neuronal excitability. In capsaicin-sensitive (CS) rat trigeminal ganglion (TG) neurons, capsaicin inhibited I-A currents in a dose-dependent manner. I-A currents were reduced 49% by 1 muM capsaicin. In capsaicin-insensitive (CIS) rat TG neurons, or small-diameter mouse VR1 -/- neurons, 1 muM capsaicin inhibited I-A currents 9 and 3%, respectively. These data suggest that in CS neurons the vast majority of the capsaicin-induced inhibition of I-A currents occurs as a consequence of the activation of vanilloid receptors. Capsaicin (1 muM) did not alter the I-A conductance-voltage relationship but shifted the inactivation-voltage curve about 15 mV to hyperpolarizing voltages, thereby increasing the number of inactivated I-A channels at the resting potential. I-A currents were relatively unaffected by 1 mM CTP-cAMP or 500 nM phorbol-12, 13-dibuterate (a protein kinase C agonist) but were inhibited by 20-30% with either 1 mM CTP-cGMP or 25 muM N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide HCl (a calcium-calmodulin kinase inhibitor). In the presence of 0.5 muM KT5823, an inhibitor of protein kinase G (PKG) pathways, 1 muM capsaicin inhibited I-A by only 26%. In summary, in CS neurons, capsaicin decreases I-A currents through the activation of vanilloid receptors. That activation, partially through the activation of cGMP-PKG and calmodulin-dependent pathways should result in increased excitability of capsaicin-sensitive nociceptors.