Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Guangzhou Street 300, Nanjing, Jiangsu Province, 210029, PR China.
Neurosci Lett. 2012 Jan 11;506(2):307-11. doi: 10.1016/j.neulet.2011.11.031. Epub 2011 Dec 1.
Migraine is increasingly recognized as a channelopathy, and abnormalities of voltage-activated ionic channels could represent the molecular basis for the altered neuronal functioning. The high-voltage-activated (HVA) Ca(2+) channels in the trigeminovascular system play a role in the pathophysiology of migraine. In the present study, effects of amitriptyline (AMT), a commonly used migraine prophylactic drug, on the HVA calcium currents (I(Ca)) were examined in mouse trigeminal ganglion neurons using whole-cell patch clamp technique. AMT produced concentration- and use-dependent inhibition of HVA I(Ca). Bath application of GÖ-6983 (a selective protein kinase C inhibitor) or H89 (a protein kinase A inhibitor) did not reduce the AMT-induced inhibition of HVA I(Ca). A similar inhibition was observed when calcium imaging was used to directly monitor the effects of AMT on KCl-induced increments of intracellular Ca(2+) concentration (Ca(2+)). By blocking HVA Ca(2+) channels and Ca(2+) entry into cells, AMT could prevent the release of neurotransmitters and help restore the neuronal threshold for excitation. Our findings suggest interesting therapeutic mechanisms for AMT in migraine prevention.
偏头痛越来越被认为是一种通道病，电压激活离子通道的异常可能代表了神经元功能改变的分子基础。三叉血管系统中的高电压激活 (HVA) Ca(2+) 通道在偏头痛的病理生理学中起作用。在本研究中，我们使用全细胞膜片钳技术，在小鼠三叉神经节神经元中，研究了阿米替林 (AMT)，一种常用的偏头痛预防药物，对 HVA 钙电流 (I(Ca)) 的影响。AMT 对 HVA I(Ca) 产生浓度和使用依赖性抑制。GÖ-6983（一种选择性蛋白激酶 C 抑制剂）或 H89（一种蛋白激酶 A 抑制剂）的浴液应用并未减少 AMT 对 HVA I(Ca) 的抑制作用。当使用钙成像直接监测 AMT 对 KCl 诱导的细胞内 Ca(2+)浓度 (Ca(2+)) 增加的影响时，观察到类似的抑制作用。通过阻断 HVA Ca(2+) 通道和 Ca(2+) 进入细胞，AMT 可以防止神经递质的释放，并有助于恢复神经元的兴奋阈值。我们的发现为 AMT 在偏头痛预防中的治疗机制提供了有趣的线索。
