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Targeting BKCa Channels in Migraine: Rationale and Perspectives

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Abstract

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.

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  1. Danish Headache Center, Department of Neurology, University of Copenhagen, Valdemar Hansen Vej 5, 2600, Glostrup, Denmark

    Mohammad Al-Mahdi Al-Karagholi, Christian Gram, Cherie Amalie Waldorff Nielsen & Messoud Ashina

  2. Glostrup Research Park, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark

    Messoud Ashina

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Messoud Ashina (MA) reports personal fees from Allergan, Amgen, Alder, Eli Lilly, Novartis and Teva. MA has no ownership interest and does not own stocks of any pharmaceutical company. MA serves as associated editor of Cephalalgia and co-editor of the Journal of Headache and Pain. MA is the President of the International Headache Society and General Secretary of the European Headache Federation. Mohammad Al-Mahdi Al-Karagholi (MMK) has acted as an invited speaker for Novartis and received travel grant from ElectroCore. Christian Gram and Cherie Amalie Waldorff Nielsen declare no conflict of interest.

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Al-Karagholi, M.AM., Gram, C., Nielsen, C.A.W. et al. Targeting BKCa Channels in Migraine: Rationale and Perspectives. CNS Drugs 34, 325–335 (2020). https://doi.org/10.1007/s40263-020-00706-8

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