Skip to main content

Advertisement

SpringerLink
Log in

Latest Insights into the Pathophysiology of Migraine: the ATP-Sensitive Potassium Channels

  • Episodic Migraine (S Nahas, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Migraine remains a challenging condition to treat, thus highlighting the need for a better understanding of its molecular mechanisms. This review intends to unravel a new emerging target in migraine pathophysiology, the adenosine 5′-triphosphate-sensitive K+ (KATP) channel.

Recent Findings

KATP channel is a common denominator in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) mediated intracellular cascades, both of which are involved in migraine. Intravenous infusion of KATP channel opener, levcromakalim, provoked migraine attack associated with dilation of extracerebral arteries in all persons with migraine.

Summary

Preclinical and clinical studies implicate KATP channels in migraine initiation. KATP channel is a novel therapeutic target for the acute and preventive treatment of migraine. Future studies are warranted to provide a better understanding of the role of KATP channel subgroups in migraine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

Not applicable.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Clemente Agostoni E, Barbanti P, Calabresi P, The Italian chronic migraine group, et al. Current and emerging evidence-based treatment options in chronic migraine: a narrative review. J Headache Pain. 2019;20. https://doi.org/10.1186/s10194-019-1038-4.

  2. Goadsby PJ, Holland PR. Migraine therapy: current approaches and new horizons. Neurotherapeutics. 2018;15:271–3.

    PubMed  PubMed Central  Google Scholar 

  3. Bohm PE, Stancampiano FF, Rozen TD. Migraine headache: updates and future developments. Mayo Clin Proc. 2018;93:1648–53.

    PubMed  Google Scholar 

  4. Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet. 2019;394:1765–74.

    PubMed  Google Scholar 

  5. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17:174–82.

    CAS  PubMed  Google Scholar 

  6. Ashina M, Hansen JM, BOÁ D, Olesen J. Human models of migraine-short-term pain for long-term gain. Nat Rev Neurol. 2017;13:713–24. https://doi.org/10.1038/nrneurol.2017.137.

    Article  PubMed  Google Scholar 

  7. Ashina M, Hansen JM, Olesen J. Pearls and pitfalls in human pharmacological models of migraine: 30 years’ experience. Cephalalgia. 2013;33:540–53.

    PubMed  Google Scholar 

  8. Schytz HW, Schoonman GG, Ashina M. What have we learnt from triggering migraine? Curr Opin Neurol. 2010;23:259–65.

    CAS  PubMed  Google Scholar 

  9. Al-Karagholi MAM, Hansen JM, Severinsen J, Jansen-Olesen I, Ashina M. The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine. J Headache Pain. 2017;18:90. https://doi.org/10.1186/s10194-017-0800-8.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Guo S, Olesen J, Ashina M. Phosphodiesterase 3 inhibitor cilostazol induces migraine-like attacks via cyclic AMP increase. Brain. 2014;137:2951–9.

    PubMed  Google Scholar 

  11. Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol. 1988;23:193–6.

    CAS  PubMed  Google Scholar 

  12. Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia. 2002;22:54–61.

    CAS  PubMed  Google Scholar 

  13. Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J. Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain. 2000;86:133–8.

    CAS  PubMed  Google Scholar 

  14. Schubert R, Serebryakov VN, Mewes H, Hopp HH. Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase. Am J Physiol Heart Circ Physiol. 1997;272:H1147–56. https://doi.org/10.1152/ajpheart.1997.272.3.h1147.

    Article  CAS  Google Scholar 

  15. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, et al. Coy DHIsolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun. 1989;164:567–74.

    CAS  PubMed  Google Scholar 

  16. Jansen-Olesen I, Mortensen A, Edvinsson L. Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase. Cephalalgia. 1996;16:310–6.

    CAS  PubMed  Google Scholar 

  17. Francis SH, Corbin JD. Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci. 1999;36:275–328.

    CAS  PubMed  Google Scholar 

  18. Al-Karagholi MAM, Hansen JM, Severinsen J, Jansen-Olesen I, Ashina M. The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine. J Headache Pain. 2017;18:1–9.

    Google Scholar 

  19. Edvinsson L, Ekman R, Jansen I, McCulloch J, Uddman R. Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects. J Cereb Blood Flow Metab. 1987;7:720–8.

    CAS  PubMed  Google Scholar 

  20. Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010;30:1179–86.

    PubMed  Google Scholar 

  21. Fahrenkrug J. PACAP-a multifacetted neuropeptide. Chronobiol Int. 2006;23(1-2):53-61. https://doi.org/10.1080/07420520500464569.

  22. Tajti J, Uddman R, Möller S, Sundler F, Edvinsson L. Messenger molecules and receptor mRNA in the human trigeminal ganglion. J Auton Nerv Syst. 1999;76:176–83.

    CAS  PubMed  Google Scholar 

  23. Syed AU, Koide M, Braas KM, May V, Wellman GC. Pituitary adenylate cyclase-activating polypeptide (PACAP) potently dilates middle meningeal arteries: implications for migraine. J Mol Neurosci. 2012;48:574–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Schytz HW, Birk S, Wienecke T, Kruuse C, Olesen J, Ashina M. PACAP38 induces migraine-like attacks in patients with migraine without aura. Brain. 2009;132:16–25.

    PubMed  Google Scholar 

  25. Ghanizada H, Al-Karagholi MA-M, Arngrim N, Olesen J, Ashina M. PACAP27 induces migraine-like attacks in migraine patients. Cephalalgia. 2020;40(1):57–67. https://doi.org/10.1177/0333102419864507.

    Article  PubMed  Google Scholar 

  26. Zhang YZ, Sjőlund B, Moller K, Håkanson R, Sundler F. Pituitary adenylate cyclase activating peptide produces a marked and long-lasting depression of a C-fibre-evoked flexion reflex. Neuroscience. 1993;57:733–7.

    CAS  PubMed  Google Scholar 

  27. Gulbenkian S, Uddman R, Edvinsson L. Neuronal messengers in the human cerebral circulation. Peptides. 2001;22:995–1007.

    CAS  PubMed  Google Scholar 

  28. Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O, et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev. 2009;61:283–357.

    CAS  PubMed  Google Scholar 

  29. Lutz EM, Sheward WJ, West KM, Morrow JA, Fink G, Harmar AJ. The VIP2 receptor: molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide. FEBS Lett. 1993;334:3–8.

    CAS  PubMed  Google Scholar 

  30. Hosoya M, Onda H, Ogi K, Masuda Y, Miyamoto Y, Ohtaki T, et al. Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Biochem Biophys Res Commun. 1993;194:133–43.

    CAS  PubMed  Google Scholar 

  31. Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine. Cephalalgia. 2008;28:226–36.

    CAS  PubMed  Google Scholar 

  32. Amin FM, Hougaard A, Schytz HW, Asghar MS, Lundholm E, Parvaiz AI, et al. Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38. Brain. 2014;137:779–94.

    PubMed  Google Scholar 

  33. Study to evaluate the efficacy and safety of AMG 301 in migraine prevention - Full Text View -ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03238781. Accessed 1 May  2020.

  34. Pellesi L, Al-Karagholi MA-M, Chaudhry BA, Lopez CL, Snellman J, Hannibal J, et al. Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers. Cephalalgia. 2020;40:1212–23. https://doi.org/10.1177/0333102420937655.

    Article  PubMed  Google Scholar 

  35. The effects of a long-lasting infusion of vasoactive intestinal peptide (VIP) in episodic migraine patients -ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04260035. Accessed 19 April 2020.

  36. Pardutz A, Schoenen J. NSAIDs in the acute treatment of migraine: a review of clinical and experimental data. Pharmaceuticals. 2010;3:1966–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Ricciotti E, Fitzgerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:986–1000.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Antonova M, Wienecke T, Olesen J, Ashina M. Prostaglandin E(2) induces immediate migraine-like attack in migraine patients without aura. Cephalalgia. 2012;32:822–33.

    PubMed  Google Scholar 

  39. Wienecke T, Olesen J, Ashina M. Discrepancy between strong cephalic arterial dilatation and mild headache caused by prostaglandin D2 (PGD2). Cephalalgia. 2011;31:65–76.

    PubMed  Google Scholar 

  40. Wienecke T, Olesen J, Ashina M. Prostaglandin I2 (epoprostenol) triggers migraine-like attacks in migraineurs. Cephalalgia. 2010;30:179–90.

    CAS  PubMed  Google Scholar 

  41. Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther. 2004;103:147–66.

    CAS  PubMed  Google Scholar 

  42. Liu Y, Shakur Y, Yoshitake M, Kambayashi JI. Cilostazol (Pletal®): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev. 2001;19:369–86.

    CAS  PubMed  Google Scholar 

  43. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109–42.

    CAS  PubMed  Google Scholar 

  44. Olesen J, Iversen HK, Thomsen LL. Nitric oxide supersensitivity: a possible molecular mechanism of migraine pain. Neuroreport. 1993;4:1027–30.

    CAS  PubMed  Google Scholar 

  45. Iversen HK, Olesen J, Tfelt-Hansen P. Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics. Pain. 1989;38:17–24.

    CAS  PubMed  Google Scholar 

  46. Hansen JM, Pedersen DL, Larsen VA, Sánchez-Del-Rio M, Alvarez Linera JR, Olesen J, et al. Magnetic resonance angiography shows dilatation of the middle cerebral artery after infusion of glyceryl trinitrate in healthy volunteers. Cephalalgia. 2007;27:118–27.

    CAS  PubMed  Google Scholar 

  47. Lassen LH, Thomsen LL, Olesen J. Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine. Neuroreport. 1995;6:1475–9.

    CAS  PubMed  Google Scholar 

  48. Faraci FM, Brian JE. Nitric oxide and the cerebral circulation. Stroke. 1994;25:692–703.

    CAS  PubMed  Google Scholar 

  49. Kruuse C, Thomsen LL, Birk S, Olesen J. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain. 2003;126:241–7.

    PubMed  Google Scholar 

  50. Christensen CE, Younis S, Lindberg U, et al. Intradural artery dilation during experimentally induced migraine attacks. [published online ahead of print, 2020 Jul 21]. Pain. 2020. https://doi.org/10.1097/j.pain.0000000000002008.

  51. Niehaus L, Gottschalk S, Weber U. Effect of drug-induced vasodilatation of basal brain arteries with nitroglycerin on blood flow velocity and volume flow in the middle cerebral artery. Ultraschall Med. 1998;19:225–9.

    CAS  PubMed  Google Scholar 

  52. Armstead WM. Role of ATP-sensitive K+ channels in cGMP-mediated pial artery vasodilation. Am J Physiol Heart Circ Physiol. 1996;270:H423–6. https://doi.org/10.1152/ajpheart.1996.270.2.h423.

    Article  CAS  Google Scholar 

  53. Hempelmann RG, Seebeck J, Kruse ML, Ziegler A, Mehdorn HM. Role of potassium channels in the relaxation induced by the nitric oxide (NO) donor DEA/NO in the isolated rat basilar artery. Neurosci Lett. 2001;313:21–4.

    CAS  PubMed  Google Scholar 

  54. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983;305:147–8.

    CAS  PubMed  Google Scholar 

  55. Schwanstecher C, Panten U. Tolbutamide- and diazoxide-sensitive K+ channel in neurons of substantia nigra pars reticulata. Naunyn Schmiedeberg's Arch Pharmacol. 1993;348:113–7.

    CAS  Google Scholar 

  56. Ashford MLJ, Sturgess NC, Trout NJ, Gardner NJ, Hales CN. Adenosine-5′-triphosphate-sensitive ion channels in neonatal rat cultured central neurones. Pflugers Arch - Eur J Physiol. 1988;412:297–304.

    CAS  Google Scholar 

  57. Bernardi H, De Weille JR, Epelbaum J, Mourre C, Amoroso S, Slama A, et al. ATP-modulated K+ channels sensitive to antidiabetic sulfonylureas are present in adenohypophysis and are involved in growth hormone release. Proc Natl Acad Sci U S A. 1993;90:1340–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989;80–245:177–80.

    Google Scholar 

  59. Ashcroft FM, Harrison DE, Ashcroft SJH. Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature. 1984;312:446–8.

    CAS  PubMed  Google Scholar 

  60. Cook DL, Hales N. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature. 1984;311:271–3.

    CAS  PubMed  Google Scholar 

  61. Chutkow WA, Makielski JC, Nelson DJ, Burant CF, Fan Z. Alternative splicing of sur2 exon 17 regulates nucleotide sensitivity of the ATP-sensitive potassium channel. J Biol Chem. 1999;274:13656–65.

    CAS  PubMed  Google Scholar 

  62. Aguilar-Bryan L, Clement JP IV, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of K(ATP) channels. Physiol Rev. 1998;78:227–45.

    CAS  PubMed  Google Scholar 

  63. Kuang Q, Purhonen P, Hebert H. Structure of potassium channels. Cell Mol Life Sci. 2015;72:3677–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Rodrigo G, Standen N. ATP-sensitive potassium channels. Curr Pharm Des. 2005;11:1915–40.

    CAS  PubMed  Google Scholar 

  65. Ploug KB, Amrutkar DV, Baun M, Ramachandran R, Iversen A, Lund TM, et al. ATP channel openers in the trigeminovascular system. Cephalalgia. 2012;32:55–65.

    CAS  PubMed  Google Scholar 

  66. Inagaki N, Seino S. ATP-sensitive potassium channels: structures, functions, and pathophysiology. Jpn J Physiol. 1998;48:397–412.

    CAS  PubMed  Google Scholar 

  67. Carrasco AJ, Dzeja PP, Alekseev AE, Pucar D, Zingman LV, Abraham MR, et al. Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels. Proc Natl Acad Sci U S A. 2001;98:7623–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Ashcroft FM, Gribble FM. Correlating structure and function in ATP-sensitive K+ channels. Trends Neurosci. 1998;21:288–94.

    CAS  PubMed  Google Scholar 

  69. Seino S, Miki T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol. 2003;81:133–76.

    CAS  PubMed  Google Scholar 

  70. Quayle JM, Nelson MT, Standen NB. ATP-sensitive and inwardly rectifying potassium channels in smooth muscle. Physiol Rev. 1997;77:1165–232.

    CAS  PubMed  Google Scholar 

  71. Faraci FM, Heistad DD. Role of ATP-sensitive potassium channels in the basilar artery. Am J Physiol Heart Circ Physiol. 1993;264:H8–H13. https://doi.org/10.1152/ajpheart.1993.264.1.h8.

    Article  CAS  Google Scholar 

  72. Nagao T, Sadoshima S, Kamouchi M, Fujishima M. Cromakalim dilates rat cerebral arteries in vitro. Stroke. 1991;22:221–4.

    CAS  PubMed  Google Scholar 

  73. McPherson GA, Stork AP. The resistance of some rat cerebral arteries to the vasorelaxant effect of cromakalim and other K+ channel openers. Br J Pharmacol. 1992;105:51–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Masuzawa K, Asano M, Matsuda T, Imaizumi Watanabe YM. Possible involvement of ATP-sensitive K+ channels in the relaxant response of dog middle cerebral artery to cromakalim. J Pharmacol Exp Ther. 1990;255:818–25.

    CAS  PubMed  Google Scholar 

  75. Iwamoto T, Nishimura N, Morita T, Sukamoto T. Differential vasorelaxant effects of K(+)-channel openers and Ca(2+)-channel blockers on canine isolated arteries. J Pharm Pharmacol. 1993;45:292–7.

    CAS  PubMed  Google Scholar 

  76. Ksoll E, Parsons AA, Mackert JRL, Schilling L, Wahl M. Analysis of cromakalim-, pinacidil-, and nicorandil-induced relaxation of the 5-hydroxytryptamine precontracted rat isolated basilar artery. Naunyn Schmiedeberg's Arch Pharmacol. 1991;343:377–83.

    CAS  Google Scholar 

  77. Ploug KB, Sørensen MA, Strøbech L, Klaerke DA, Hay-Schmidt A, Sheykhzade M, et al. KATP channels in pig and human intracranial arteries. Eur J Pharmacol. 2008;601:43–9.

    CAS  PubMed  Google Scholar 

  78. Jahangir A, Terzic A. KATP channel therapeutics at the bedside. J Mol Cell Cardiol. 2005;39:99–112.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Mannhold R. KATP channel openers: structure-activity relationships and therapeutic potential. Med Res Rev. 2004;24:213–66.

    CAS  PubMed  Google Scholar 

  80. Gribble FM, Reimann F. Sulphonylurea action revisited: the post-cloning era. Diabetologia. 2003;46:875–91.

    CAS  PubMed  Google Scholar 

  81. Roland E. Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. Eur Heart J. 1993;14:48–52.

    PubMed  Google Scholar 

  82. Thomas P, Dixon M, Winterton S, Sheridan D. Acute haemodynamic effects of cromakalim in patients with angina pectoris. Br J Clin Pharmacol. 1993;29:325–31.

    Google Scholar 

  83. Williams AJ, Lee TH, Vyse T, Chiew F, Cochrane GM, Williams AJ, et al. Attenuation of nocturnal asthma by cromakalim. Lancet. 1990;336:334–6.

    CAS  PubMed  Google Scholar 

  84. Kidney JC, Fuller RW, Worsdell YM, Lavender EA, Chung KF, Barnes PJ. Effect of an oral potassium channel activator, BRL 38227, on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol. Thorax. 1993;48:130–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Al-Karagholi MA, Ghanizada H, Hansen JM, Skovgaard LT, Olesen J, Larsson HBW, et al. Levcromakalim, an adenosine triphosphate-sensitive potassium channel opener, dilates extracerebral but not cerebral arteries. Headache. 2019;59:1468–80.

    PubMed  Google Scholar 

  86. •• Al-Karagholi MAM, Hansen JM, Guo S, Olesen J, Ashina M. Opening of ATP-sensitive potassium channels causes migraine attacks: a new target for the treatment of migraine. Brain. 2019;142:2644–54. Important study supporting the importance of KATP channels in migraine.

  87. Al-Karagholi MAM, Ghanizada H, Hansen JM, Aghazadeh S, Skovgaard LT, Olesen J, et al. Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects. Cephalalgia. 2019;39:1789–97.

    PubMed  Google Scholar 

  88. Barbanti P, Egeo G. Mitsikostas DDTrigeminal-targeted treatments in migraine: is 60% the magic number? Headache. 2019;59:1659–61.

    PubMed  Google Scholar 

  89. Glibenclamide: a review. Drugs. 1971;1:116–40. https://doi.org/10.2165/00003495-197101020-00002.

  90. •• Christensen SL, Munro G, Petersen S, Shabir A, Jansen-Olesen I, Kristensen DM, et al. ATP sensitive potassium (KATP) channel inhibition: a promising new drug target for migraine. Cephalalgia. 2020. https://doi.org/10.1177/0333102420925513. Study supporting a possible role for KATP channel blockers in migraine treatment.

  91. •• Gozalov A, Jansen-Olesen I, Klaerke D, Olesen J. Role of KATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat. Headache. 2008;48:1202–13. Important study supporting the importance of KATP channels in migraine.

  92. Bruch L, Rubel S, Kästner A, Gellert K, Gollasch M, Witt C. Pituitary adenylate cyclase activating peptides relax human pulmonary arteries by opening of K(ATP) and K(CA) channels. Thorax. 1998;53:586–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. MAM Al‐Karagholi H, Ghanizada L, Kokoti Paulsen JS, Hansen JM, Ashina M. Effect of K channel blocker glibenclamide on levcromakalim-induced headache. Cephalalgia 2020;40(10):1045–54.

  94. Ashford MLJ, Boden PR, Treherne JM. Glucose-induced excitation of hypothalamic neurones is mediated by ATP-sensitive K+ channels. Pflugers Arch - Eur J Physiol. 1990;415:479–83.

    CAS  Google Scholar 

  95. Röper J, Ashcroft FM. Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones. Pflugers Arch - Eur J Physiol. 1995;430:44–54.

    Google Scholar 

  96. Ohno-Shosaku T, Yamamoto C. Identification of an ATP-sensitive K+ channel in rat cultured cortical neurons. Pflugers Arch. 1992;422:260–6.

    CAS  PubMed  Google Scholar 

  97. Häusser MA, de Weille JR, Lazdunski M. Activation by cromakalim of pre- and post-synaptic ATP-sensitive K+ channels in substantia nigra. Biochem Biophys Res Commun. 1991;174:909–14.

    PubMed  Google Scholar 

  98. Maneuf YP, Duty S, Hille CJ, Crossman AR, Brotchie JM. Modulation of GABA transmission by diazoxide and cromakalim in the globus pallidus: implications for the treatment of Parkinson’s disease. Exp Neurol. 1996;139:12–6.

    CAS  PubMed  Google Scholar 

  99. Hoffmann J, Charles A. Glutamate and its receptors as therapeutic targets for migraine. Neurotherapeutics. 2018;15:361–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Yee AG, Lee SM, Hunter MR, Glass M, Freestone PS, Lipski J. Effects of the Parkinsonian toxin MPP+ on electrophysiological properties of nigral dopaminergic neurons. Neurotoxicology. 2014;45:1–11.

    CAS  PubMed  Google Scholar 

  101. Kyle BD, Hurst S, Swayze RD, Sheng J, Braun AP. Specific phosphorylation sites underlie the stimulation of a large conductance, Ca2+−activated K+ channel by cGMP-dependent protein kinase. FASEB J. 2013;27:2027–38.

    CAS  PubMed  Google Scholar 

  102. So YP, Jeong HL, Chi DK, Won SL, Won SP, Han J, et al. Cilostazol suppresses superoxide production and expression of adhesion molecules in human endothelial cells via mediation of cAMP-dependent protein kinase-mediated maxi-K channel activation. J Pharmacol Exp Ther. 2006;317:1238–45.

    Google Scholar 

  103. Wulf-Johansson H, Amrutkar DV, Hay-Schmidt A, Poulsen AN, Klaerke DA, Olesen J, et al. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway. Neuroscience. 2010;167:1091–102.

    CAS  PubMed  Google Scholar 

  104. Wang Y, Mathers DA. Ca(2+)-Dependent K+ channels of high conductance in smooth muscle cells isolated from rat cerebral arteries. J Physiol. 1993;462:529–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Al-Karagholi MAM, Gram C, Nielsen CAW, Ashina M. Targeting BKCa channels in migraine: rationale and perspectives. CNS Drugs. 2020;34:325–35.

    CAS  PubMed  Google Scholar 

  106. MAM Al‐Karagholi H, Ghanizada L, Kokoti Paulsen JS, Hansen JM, Ashina M. Opening of BK channels alters cerebral hemodynamic and causes headache in healthy volunteers . Cephalalgia 2020;40(11):1145–54.

Download references

Author information

Authors and Affiliations

  1. Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Valdemar Hansen Vej 5, Glostrup, DK-2600, Copenhagen, Denmark

    Lili Kokoti, Mohammad Al-Mahdi Al-Karagholi & Messoud Ashina

  2. Danish Headache Knowledge Center, Rigshospitalet – Glostrup, Valdemar Hansens Vej 5, DK-2600, Glostrup, Denmark

    Messoud Ashina

Authors
  1. Lili Kokoti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Al-Mahdi Al-Karagholi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Messoud Ashina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Messoud Ashina.

Ethics declarations

Conflict of Interest

MMK has acted as an invited speaker for Novartis and received travel grant from ElectroCore, LLC. MA is a consultant, speaker, or scientific advisor for Allergan, Amgen, Alder, ATI, Eli Lilly, Lundbeck, Novartis, and Teva; primary investigator for Alder, Amgen, Allergan, Eli Lilly, Novartis, and Teva trials. MA has no ownership interest and does not own stocks of any pharmaceutical company. MA serves as associate editor of Cephalalgia; associate editor of Headache; associate editor of the Journal of Headache and Pain. MA is President of the International Headache Society. LK declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Ethics Approval

Not applicable

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Code Availability

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Episodic Migraine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kokoti, L., Al-Karagholi, M.AM. & Ashina, M. Latest Insights into the Pathophysiology of Migraine: the ATP-Sensitive Potassium Channels. Curr Pain Headache Rep 24, 77 (2020). https://doi.org/10.1007/s11916-020-00911-6

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11916-020-00911-6

Keywords

Search

Navigation