Glostrup Research Institute, Department of Neurology, Danish Headache Center, Copenhagen University Hospital-Rigshospitalet, Nordstjernevej 42, Glostrup, 2600 Copenhagen, Denmark.
Department of Odontology, Panum Institute, Faculty of Health, University of Copenhagen, 2300 Copenhagen, Denmark.
Cells. 2022 Aug 4;11(15):2406. doi: 10.3390/cells11152406.
Globally, migraine is a leading cause of disability with a huge impact on both the work and private life of affected persons. To overcome the societal migraine burden, better treatment options are needed. Increasing evidence suggests that ATP-sensitive potassium (K) channels are involved in migraine pathophysiology. These channels are essential both in blood glucose regulation and cardiovascular homeostasis. Experimental infusion of the K channel opener levcromakalim to healthy volunteers and migraine patients induced headache and migraine attacks in 82-100% of participants. Thus, this is the most potent trigger of headache and migraine identified to date. Levcromakalim likely induces migraine via dilation of cranial arteries. However, other neuronal mechanisms are also proposed. Here, basic K channel distribution, physiology, and pharmacology are reviewed followed by thorough review of clinical and preclinical research on K channel involvement in migraine. K channel opening and blocking have been studied in a range of preclinical migraine models and, within recent years, strong evidence on the importance of their opening in migraine has been provided from human studies. Despite major advances, translational difficulties exist regarding the possible anti-migraine efficacy of K channel blockage. These are due to significant species differences in the potency and specificity of pharmacological tools targeting the various K channel subtypes.
在全球范围内，偏头痛是导致残疾的主要原因之一，对患者的工作和私人生活都有巨大影响。为了克服偏头痛带来的社会负担，需要更好的治疗选择。越来越多的证据表明，三磷酸腺苷敏感性钾 (K) 通道参与偏头痛的病理生理学。这些通道在血糖调节和心血管稳态中都至关重要。实验性地向健康志愿者和偏头痛患者输注 K 通道开放剂 levcromakalim，会导致 82-100%的参与者出现头痛和偏头痛发作。因此，这是迄今为止发现的最有效的头痛和偏头痛触发因素。Levcromakalim 可能通过扩张颅动脉引起偏头痛。然而，也提出了其他神经元机制。本文首先综述了基本的 K 通道分布、生理学和药理学，然后对 K 通道参与偏头痛的临床前和临床研究进行了全面回顾。K 通道的开放和阻断已在一系列偏头痛的临床前模型中进行了研究，近年来，从人类研究中提供了关于其在偏头痛中的重要性的有力证据。尽管取得了重大进展，但在 K 通道阻断的抗偏头痛疗效方面仍存在转化困难。这是由于针对各种 K 通道亚型的药理学工具的效力和特异性在不同物种之间存在显著差异。
