白细胞介素-1β对三叉神经节细胞河豚毒素敏感性钠电流的双相调节作用

应用全细胞膜片钳技术记录急性分离的小鼠三叉神经节细胞电压门控性钠通道电流,观察白细胞介素-1β对河豚毒素敏感性钠电流的影响,拟从离子通道水平探讨白细胞介素-1β调节颜面部痛的分子机制.结果发现白细胞介素-1β双相调节三叉神经节细胞河豚毒素敏感性钠通道,低浓度白细胞介素-1β(1ng/mL和10ng/mL)抑制三叉神经节细胞河豚毒素敏感性钠电流锋值,其中1ng/mL白细胞介素-1β使河豚毒素敏感性钠通道半失活电压向超极化方向偏移,复活时间常数延长.高浓度白细胞介素-1β(100ng/mL)在给药即刻增强三叉神经节细胞河豚毒素敏感性钠电流锋值,使河豚毒素敏感性钠通道半激活电压向超极化方向偏移,而不影响其失活及复活特性.高、低浓度白细胞介素-1β对三叉神经节细胞河豚毒素敏感性钠电流锋值的效应具有可逆性特点.结果表明白细胞介素-1β双相调节三叉神经节细胞河豚毒素敏感性钠通道,可部分解释白细胞介素-1β双相调节痛觉的产生及对神经元的损害和保护双相效应.

Dual Modulation of Interleukin-1 Beta on Tetrodotoxin-Sensitive Sodium Currents in Mice Trigeminal Ganglion Cells

Using whole-cell patch clamp technique on the membrane of freshly isolated trigeminal ganglion (TG)neurons, the effects of recombinant human interleukin-1β(rhIL-1 β) on TTX-sensitive (TTX-S) voltage-gated sodium currents were observed to investigate its molecular mechanism in the modulation of orofacial nociceptive processing. The experimental data demonstrated that rhIL-1 β had dual effects on TTX-S sodium channels.Compared to the effects of external solution on Peak TTX-S sodium currents in TG neurons (from 100% to 104.62±4.35%), Peak TTX-S sodium currents decreased significantly after application of 1ng/mL rhIL-1β(from 100%to 54. 69±5.53%, n=14,P＜0.05) and 10ng/mL rhIL-1β(from 100% to 79.4.±8.73%, n=9,P＜0.05)respectively, while peak TTX-sensitive (TTX-S) sodium currents increased significantly after application of 100ng/mL rhIL-1β(from 100% to 120. 96±6.72%, n=14,P＜0.05). Both inhibited effects of 1ng/mL rhIL-1 β and potentiated effects of 100ng/mL rhIL-1β on TTX-S sodium currents showed reversible. The steady-state inactivation curve shifted toward the left and the steady-state recovery curve shifted toward the right after application of 1ng/mL rhIL-1 β,while the steady-state activation curve shifted toward the left after application of 100ng/mL rhIL-1 β. The dual effects of interleukin-1 beta on TTX-S sodium currents in TG cells could partly explain its dual modulation of nociceptive processing and dual protection of neurons.