BackgroundMigraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear.MethodsA rat model of conscious migraine was established through the electrical stimulation (ES) of the dural mater surrounding the superior sagittal sinus. Using patch clamp recording, immunofluorescent labelling, enzyme-linked immunosorbent assays and western blot analysis, we studied the effects of ES on sensory neuronal excitability and elucidated the underlying mechanisms mediated by voltage-gated ion channels.ResultsThe calcitonin gene-related peptide (CGRP) level in the jugular vein blood and the number of CGRP-positive neurons in the trigeminal ganglia (TGs) were significantly increased in rats with ES-induced migraine. The application of ES increased actional potential firing in both small-sized IB4-negative (IB4−) and IB4+ TG neurons. No significant changes in voltage-gated Na+ currents were observed in the ES-treated groups. ES robustly suppressed the transient outward K+ current (IA) in both types of TG neurons, while the delayed rectifier K+ current remained unchanged. Immunoblot analysis revealed that the protein expression of Kv4.3 was significantly decreased in the ES-treated groups, while Kv1.4 remained unaffected. Interestingly, ES increased the P/Q-type and T-type Ca2+ currents in small-sized IB4− TG neurons, while there were no significant changes in the IB4+ subpopulation of neurons.ConclusionThese results suggest that ES decreases the IA in small-sized TG neurons and increases P/Q- and T-type Ca2+ currents in the IB4− subpopulation of TG neurons, which might contribute to neuronal hyperexcitability in a rat model of ES-induced migraine.

中文翻译：

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上矢状窦的电刺激抑制大鼠三叉神经节神经元的 A 型 K+ 电流并增加 P/Q 和 T 型 Ca2+ 电流

背景偏头痛是一种使人衰弱的神经系统疾病，涉及三叉神经血管异常激活和敏化。然而，其潜在的细胞和分子机制仍不清楚。方法通过电刺激（ES）围绕上矢状窦的硬脑膜建立大鼠清醒偏头痛模型。使用膜片钳记录、免疫荧光标记、酶联免疫吸附试验和蛋白质印迹分析，我们研究了 ES 对感觉神经元兴奋性的影响，并阐明了电压门控离子通道介导的潜在机制。结果降钙素基因相关肽 (CGRP) ES 诱导的偏头痛大鼠颈静脉血中的 CGRP 水平和三叉神经节 (TG) 中 CGRP 阳性神经元的数量显着增加。ES 的应用增加了小型 IB4 阴性 (IB4-) 和 IB4+ TG 神经元的动作电位放电。在 ES 治疗组中未观察到电压门控 Na+ 电流的显着变化。ES 有力地抑制了两种类型的 TG 神经元中的瞬态外向 K+ 电流 (IA)，而延迟整流器 K+ 电流保持不变。免疫印迹分析显示，ES 治疗组中 Kv4.3 的蛋白表达显着降低，而 Kv1.4 未受影响。有趣的是，ES 增加了小尺寸 IB4− TG 神经元的 P/Q 型和 T 型 Ca2+ 电流，而神经元的 IB4+ 亚群没有显着变化。结论这些结果表明 ES 降低了小尺寸的 IA TG 神经元并增加 TG 神经元的 IB4− 亚群中的 P/Q 和 T 型 Ca2+ 电流，