Large (big)-conductance calcium-activated potassium (BKCa) channels are expressed in migraine-related structures such as the cranial arteries, trigeminal ganglion and trigeminal spinal nucleus, and they play a substantial role in vascular tonus and neuronal excitability. Using synthetic BKCa channels openers was associated with headache as a frequent adverse effect in healthy volunteers. Additionally, BKCa channels are downstream molecules in migraine signalling pathways that are activated by several compounds known to provoke migraine, including calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP) and glyceryl trinitrate (GTN). Also, there is a high affinity and a close coupling between BKCa channels and ATP-sensitive potassium (KATP) channels, the role of which has recently been established in migraine pathophysiology. These observations raise the question as to whether direct BKCa channel activation can provoke migraine in migraine patients, and whether the BKCa channel could be a potential novel anti-migraine target. Hence, randomized and placebo-controlled clinical studies on BKCa channel openers or blockers in migraine patients are needed.

中文翻译：

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针对偏头痛的BKCa渠道：基本原理和观点。

大（大）电导钙激活钾（BKCa）通道在与偏头痛相关的结构中表达，例如颅动脉，三叉神经节和三叉神经脊核，它们在血管紧张度和神经元兴奋性中起重要作用。在健康志愿者中，使用合成的BKCa通道开放剂与头痛相关，是常见的不良反应。此外，BKCa通道是偏头痛信号传导途径中的下游分子，被已知​​引起偏头痛的几种化合物激活，包括降钙素基因相关肽（CGRP），垂体腺苷酸环化酶激活多肽（PACAP）和三硝酸甘油酯（GTN）。此外，BKCa通道与ATP敏感钾（KATP）通道之间具有很高的亲和力并紧密耦合，最近在偏头痛病理生理学中已确定了其作用。这些观察结果提出了一个问题，即直接BKCa通道激活是否可以引起偏头痛患者的偏头痛，以及BKCa通道是否可能成为潜在的新型抗偏头痛靶标。因此，需要对偏头痛患者的BKCa通道开放剂或阻断剂进行随机且安慰剂对照的临床研究。