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. 2017 Aug 23;18(1):90.
doi: 10.1186/s10194-017-0800-8.

The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine

Mohammad Al-Mahdi Al-Karagholi  1 , Jakob Møller Hansen  1 , Johanne Severinsen  1 , Inger Jansen-Olesen  1   2 , Messoud Ashina  3
Affiliations

The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine

Mohammad Al-Mahdi Al-Karagholi et al. J Headache Pain. .

Abstract

Background: To review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine.

Discussion: KATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP channel openers can provoke migraine in migraine sufferers is not known.

Conclusion: We suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target.

Keywords: Cromakalim; Headache; KATP channel; KATP channels; Levcromakalim; Migraine.

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Conflict of interest statement

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Molecular structure and isoforms. a Two major Kir6.x isoforms (Kir6.1 and Kir 6.2) and three major SUR isoforms (SUR1, SUR2A and SUR 2B) have been identified. b Kir.x subunits combine tissue-specifically with different SUR subunits to form various native KATP channels. Pancreatic, cardiac and smooth muscle KATP channels are made up of Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.1 (or Kir6.2)/SUR2B, respectively [2]. Kir, inwardly rectifying K+ channels; SUR, sulfonylurea receptor
Fig. 2
Fig. 2
Schematic diagram of the KATP channel. Kir6.x subunits have two transmembrane domains, and a large cytoplasmic domain including an inhibitory binding site for ATP [8, 84]. SUR subunits have many transmembrane domains and two intracellular nucleotide binding domains (NBD1 and NBD2), which stimulate opening of the channel after binding to MgADP [85]
Fig. 3
Fig. 3
Opening of vascular ATP sensitive K channels. Endogenous molecules (ATP, cAMP and cGMP) and exogenous pharmacological agents (cromakalim and glibenclamide) regulate the activity of KATP channels, which help controlling the vascular tone
Fig. 4
Fig. 4
Signaling pathways through vascular smooth muscle KATP channels. Numerous endogenous vasodilators activate vascular smooth muscle KATP channels through adenylate cyclase and PKA phosphorylation. Conversely, endogenous vasoconstrictors inhibit vascular smooth muscle KATP channels through DAG and PKC phosphorylation. CGRP, calcitonin gene-related peptide; PGI2, prostaglandin I2; VIP, vasoactive intestinal peptide; AngII, angiotensin II; NPY, neuropeptide Y; NA, noradrenaline; 5-HT, 5-hydroxytryptamine; Gs, G-protein-coupled receptor alpha stimulation; Gi, G-protein-coupled receptor alpha i/q; DAG, diacylglycerol; PKA and PKC, protein kinase A and C, respectively
See this image and copyright information in PMC

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