Department of Neurology and Danish Headache Center, Glostrup Research Institute, Glostrup Hospital, Faculty of Health Sciences, University of Copenhagen, Nordre Ringvej 69, 2600 Glostrup, Denmark.
Neuroscience. 2011 Jan 13;172:510-7. doi: 10.1016/j.neuroscience.2010.10.032. Epub 2010 Oct 16.
Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are involved in the release of these peptides to different stimuli. We have examined the presence and importance of VGCCs in controlling the CGRP release from rat dura mater, freshly isolated trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Each of the four VGCCs, P/Q-, N-, and L- and T-type are abundantly found in TG and TNC relative to the dura mater and each mediates a significant fraction of high potassium concentration induced CGRP release. In dura mater, blockade of P/Q-, N- and L-type VGCCs by ω-agatoxin TK, ω-conotoxin GVIA and nimodipine at 1 μM respectively, significantly decreased the potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ω-conotoxin GVIA inhibited the potassium induced CGRP release significantly. In the absence of Ca2+ and in the presence of a cocktail of blockers the stimulated CGRP release was significantly reduced. In the TNC only the cocktail of blockers and the absence of Ca2+ could reduce the potassium induced release significantly. These results suggest that depolarization by high potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels.
临床和遗传研究表明电压门控钙通道（VGCCs）在偏头痛的发病机制中起作用。降钙素基因相关肽（CGRP）从三叉神经神经元的释放也与偏头痛有关。VGCCs 位于神经元的突触前，参与这些肽类对不同刺激的释放。我们已经检查了 VGCCs 在控制大鼠硬脑膜、新鲜分离的三叉神经节（TG）和三叉神经尾核（TNC）中 CGRP 释放中的存在和重要性。相对于硬脑膜，每个 VGCC（P/Q-、N-和 L-和 T-型）在 TG 和 TNC 中都大量存在，并且每种类型都介导了高钾浓度诱导的 CGRP 释放的显著部分。在硬脑膜中，分别用 1μM 的 ω-鹅膏蕈碱 TK、ω-芋螺毒素 GVIA 和尼莫地平阻断 P/Q-、N-和 L-型 VGCC，可显著减少钾诱导的 CGRP 释放。在没有钙离子（Ca2+）的情况下，并在阻断剂鸡尾酒的存在下，硬脑膜刺激的 CGRP 释放减少到与基础 CGRP 释放几乎相同的水平。在 TG 中，ω-芋螺毒素 GVIA 显著抑制钾诱导的 CGRP 释放。在没有 Ca2+和阻断剂鸡尾酒的情况下，刺激的 CGRP 释放显著减少。在 TNC 中，只有阻断剂鸡尾酒和没有 Ca2+才能显著减少钾诱导的释放。这些结果表明，高钾去极化释放 CGRP，释放受钙离子和电压门控钙通道调节。
