ROLE FOR VOLTAGE GATED CALCIUM CHANNELS IN CALCITONIN GENE-RELATED PEPTIDE RELEASE IN THE RAT TRIGEMINOVASCULAR SYSTEM
ROLE FOR VOLTAGE GATED CALCIUM CHANNELS IN CALCITONIN GENE-RELATED PEPTIDE RELEASE IN THE RAT TRIGEMINOVASCULAR SYSTEM
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DOI：
10.1016/j.neuroscience.2010.10.032
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发表时间：
2011-01-13
期刊：
影响因子：
3.3
通讯作者：
Jansen-Olesen, I.
中科院分区：
文献类型：
--
作者：
Amrutkar, D. V.;Ploug, K. B.;Jansen-Olesen, I.
临床和遗传学研究表明，电压门控钙通道（VGCC）在偏头痛的发病机制中发挥作用。降钙素基因相关肽（CGRP）从三叉神经元的释放也与偏头痛有关。VGCC位于突触前神经元上，并参与这些肽对不同刺激的释放。我们研究了VGCCs在控制大鼠硬脑膜、新鲜分离的三叉神经节（TG）和三叉神经尾侧核（TNC）CGRP释放中的存在和重要性。四个VGCC中的每一个，P/Q-，N-，L-和T-型在TG和TNC中相对于硬脑膜大量存在，并且每个VGCC都介导高钾浓度诱导的CGRP释放的显著部分。在硬脑膜中，阻断P/Q-，N-和L-型VGCCs的ω-agatoxin TK，ω-芋螺毒素GVIA和尼莫地平在1 μ M，分别显着降低钾诱导的CGRP释放。在钙离子（Ca 2+）的情况下，并在存在的鸡尾酒的阻滞剂，刺激的CGRP释放从硬脑膜减少到几乎相同的水平作为基础CGRP释放。在TG中，ω-芋螺毒素GVIA显著抑制钾诱导的CGRP释放。在不存在Ca 2+和存在的鸡尾酒的阻滞剂的刺激CGRP释放显着减少。在TNC中，只有阻断剂的鸡尾酒和不存在Ca 2+可以显著减少钾诱导的释放。提示高钾去极化可释放CGRP，且这种释放受Ca ~（2+）和电压门控性钙通道的调节。(C)2011年IBRO。由爱思唯尔有限公司出版。保留所有权利。
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 omega-agatoxin TK, omega-conotoxin GVIA and nimodipine at 1 mu M 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 omega-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. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.