Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons
Electrical stimulation of the superior sagittal sinus suppresses A-type K+ currents and increases P/Q- and T-type Ca2+ currents in rat trigeminal ganglion neurons
复制标题
电刺激上矢状窦可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
DOI：
10.1186/s10194-019-1037-5
复制
发表时间：
2019-08-02
影响因子：
7.4
通讯作者：
Tao, Jin
中科院分区：
文献类型：
--
作者：
Cao, Junping;Zhang, Yuan;Tao, Jin
背景 偏头痛是一种使人衰弱的神经系统疾病，涉及异常的三叉血管激活和敏化。然而，潜在的细胞和分子机制仍不清楚。方法通过电刺激上矢状窦周围硬脑膜建立清醒偏头痛大鼠模型。利用膜片钳记录、免疫荧光标记、酶联免疫吸附测定和蛋白质印迹分析，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ES诱发偏头痛的大鼠颈静脉血中降钙素基因相关肽（CGRP）水平和三叉神经节（TG）中CGRP阳性神经元数量显着增加。 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。 ES 处理组中未观察到电压门控 Na+ 电流的显着变化。 ES 强有力地抑制了两种类型 TG 神经元中的瞬时外向 K+ 电流 (I-A)，而延迟整流 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不受影响。有趣的是，ES增加了小尺寸IB4-TG神经元中的P/Q型和T型Ca2+电流，而IB4+神经元亚群没有显着变化。结论 这些结果表明，ES 降低了小型 TG 神经元中的 I-A，并增加了 TG 神经元 IB4- 亚群中的 P/Q- 和 T 型 Ca2+ 电流，这可能导致 ES 诱导的偏头痛大鼠模型中神经元过度兴奋。
Background Migraine is a debilitating neurological disorder involving abnormal trigeminovascular activation and sensitization. However, the underlying cellular and molecular mechanisms remain unclear. Methods A 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. Results The 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 (I-A) 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. Conclusion These results suggest that ES decreases the I-A 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.