{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:48:06Z","timestamp":1788994086929,"version":"build-2803163510"},"reference-count":181,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Candys Foundation","award":["NNF20SA0064340"],"award-info":[{"award-number":["NNF20SA0064340"]}]},{"name":"Novo Nordisk Foundation","award":["NNF20SA0064340"],"award-info":[{"award-number":["NNF20SA0064340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 (KATP) channels are involved in migraine pathophysiology. These channels are essential both in blood glucose regulation and cardiovascular homeostasis. Experimental infusion of the KATP 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 KATP channel distribution, physiology, and pharmacology are reviewed followed by thorough review of clinical and preclinical research on KATP channel involvement in migraine. KATP 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 KATP channel blockage. These are due to significant species differences in the potency and specificity of pharmacological tools targeting the various KATP channel subtypes.<\/jats:p>","DOI":"10.3390\/cells11152406","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T21:52:48Z","timestamp":1659649968000},"page":"2406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["ATP-Sensitive Potassium Channels in Migraine: Translational Findings and Therapeutic Potential"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-9291","authenticated-orcid":false,"given":"Amalie","family":"Clement","sequence":"first","affiliation":[{"name":"Glostrup Research Institute, Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, Nordstjernevej 42, Glostrup, 2600 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Guo","sequence":"additional","affiliation":[{"name":"Glostrup Research Institute, Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, Nordstjernevej 42, Glostrup, 2600 Copenhagen, Denmark"},{"name":"Department of Odontology, Panum Institute, Faculty of Health, University of Copenhagen, 2300 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Jansen-Olesen","sequence":"additional","affiliation":[{"name":"Glostrup Research Institute, Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, Nordstjernevej 42, Glostrup, 2600 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-4783","authenticated-orcid":false,"given":"Sarah Louise","family":"Christensen","sequence":"additional","affiliation":[{"name":"Glostrup Research Institute, Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet, Nordstjernevej 42, Glostrup, 2600 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s10194-020-01208-0","article-title":"Migraine Remains Second among the World\u2019s Causes of Disability, and First among Young Women: Findings from GBD2019","volume":"21","author":"Steiner","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd Edition","volume":"38","author":"Olesen","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1111\/head.13358","article-title":"Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology Mechanisms","volume":"58","author":"Vgontzas","year":"2018","journal-title":"Headache"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s10194-018-0933-4","article-title":"Cognitive Dysfunction and Migraine 17 Psychology and Cognitive Sciences 1701 Psychology 11 Medical and Health Sciences 1103 Clinical Sciences 11 Medical and Health Sciences 1109 Neurosciences","volume":"19","author":"Vuralli","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(20)32160-7","article-title":"Migraine: Epidemiology and Systems of Care","volume":"397","author":"Ashina","year":"2021","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1056\/NEJMra1915327","article-title":"Migraine","volume":"383","author":"Ashina","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","article-title":"Migraine and the Trigeminovascular System-40 Years and Counting","volume":"18","author":"Ashina","year":"2019","journal-title":"Lancet. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1097\/j.pain.0000000000001531","article-title":"Migraine Understood as a Sensory Threshold Disease","volume":"160","author":"Peng","year":"2019","journal-title":"Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","article-title":"CGRP as the Target of New Migraine Therapies\u2014Successful Translation from Bench to Clinic","volume":"14","author":"Edvinsson","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1001\/jamaneurol.2018.1212","article-title":"Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial","volume":"75","author":"Stauffer","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s10194-018-0951-2","article-title":"Preventive Effects of Galcanezumab in Adult Patients with Episodic or Chronic Migraine Are Persistent: Data from the Phase 3, Randomized, Double-Blind, Placebo-Controlled EVOLVE-1, EVOLVE-2, and REGAIN Studies","volume":"19","author":"Zhang","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1111\/ene.14715","article-title":"Long-Term Efficacy and Safety of Erenumab in Migraine Prevention: Results from a 5-Year, Open-Label Treatment Phase of a Randomized Clinical Trial","volume":"28","author":"Ashina","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1056\/NEJMoa1709038","article-title":"Fremanezumab for the Preventive Treatment of Chronic Migraine","volume":"377","author":"Silberstein","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/0333102420905132","article-title":"Eptinezumab in Episodic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study (PROMISE-1)","volume":"40","author":"Ashina","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1046\/j.1468-2982.2002.00310.x","article-title":"CGRP May Play a Causative Role in Migraine","volume":"22","author":"Lassen","year":"2002","journal-title":"Cephalalgia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/brain\/awn307","article-title":"PACAP38 Induces Migraine-like Attacks in Patients with Migraine without Aura","volume":"132","author":"Schytz","year":"2009","journal-title":"Brain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1046\/j.1468-2982.1997.1708873.x","article-title":"Investigations into the Role of Nitric Oxide and the Large Intracranial Arteries in Migraine Headache","volume":"17","author":"Thomsen","year":"1997","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1177\/0333102420937655","article-title":"Two-Hour Infusion of Vasoactive Intestinal Polypeptide Induces Delayed Headache and Extracranial Vasodilation in Healthy Volunteers","volume":"40","author":"Pellesi","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/brain\/awg009","article-title":"Migraine Can Be Induced by Sildenafil without Changes in Middle Cerebral Artery Diameter","volume":"126","author":"Kruuse","year":"2003","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1093\/brain\/awu244","article-title":"Phosphodiesterase 3 Inhibitor Cilostazol Induces Migraine-like Attacks via Cyclic AMP Increase","volume":"137","author":"Guo","year":"2014","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1093\/brain\/awz199","article-title":"Opening of ATP-Sensitive Potassium Channels Causes Migraine Attacks: A New Target for the Treatment of Migraine","volume":"142","author":"Hansen","year":"2019","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1093\/brain\/awab136","article-title":"Opening of ATP Sensitive Potassium Channels Causes Migraine Attacks with Aura","volume":"144","author":"Ghanizada","year":"2021","journal-title":"Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/305147a0","article-title":"ATP-Regulated K+ Channels in Cardiac Muscle","volume":"305","author":"Noma","year":"1983","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1677\/jme.0.0220113","article-title":"The Structure and Function of the ATP-Sensitive K+ Channel in Insulin-Secreting Pancreatic Beta-Cells","volume":"22","author":"Miki","year":"1999","journal-title":"J. Mol. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pbiomolbio.2008.10.002","article-title":"Modeling KATP Channel Gating and Its Regulation","volume":"99","author":"Proks","year":"2009","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1152\/physrev.00021.2009","article-title":"Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles","volume":"90","author":"Hibino","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s10863-009-9233-7","article-title":"Single Channel Studies of the ATP-Regulated Potassium Channel in Brain Mitochondria","volume":"41","author":"Choma","year":"2009","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1146\/annurev.physiol.60.1.667","article-title":"A View of Sur\/Kir6.X, KATP Channels","volume":"60","author":"Babenko","year":"1998","journal-title":"Annu. Rev. Physiol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0079-6107(02)00053-6","article-title":"Physiological and Pathophysiological Roles of ATP-Sensitive K+ Channels","volume":"81","author":"Seino","year":"2003","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1177\/0271678X17749392","article-title":"Tonic Regulation of Middle Meningeal Artery Diameter by ATP-Sensitive Potassium Channels","volume":"39","author":"Syed","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.2501869","article-title":"Hyperpolarizing Vasodilators Activate ATP-Sensitive K+ Channels in Arterial Smooth Muscle","volume":"245","author":"Standen","year":"1989","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sung, M.W., Yang, Z., Driggers, C.M., Patton, B.L., Mostofian, B., Russo, J.D., Zuckerman, D.M., and Shyng, S.L. (2021). Vascular KATP Channel Structural Dynamics Reveal Regulatory Mechanism by Mg-Nucleotides. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2109441118"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yjmcc.2004.11.018","article-title":"Regulation of the ATP-Sensitive K Channel Kir6.2 by ATP and PIP(2)","volume":"39","author":"Ribalet","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1126\/science.282.5391.1141","article-title":"PIP2 and PIP as Determinants for ATP Inhibition of KATP Channels","volume":"282","author":"Baukrowitz","year":"1998","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.2337\/diabetes.49.9.1409","article-title":"Phosphatidylinositol 4,5-Bisphosphate and ATP-Sensitive Potassium Channel Regulation: A Word of Caution","volume":"49","author":"Larsson","year":"2000","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1074\/jbc.M708769200","article-title":"A Short Motif in Kir6.1 Consisting of Four Phosphorylation Repeats Underlies the Vascular KATP Channel Inhibition by Protein Kinase C","volume":"283","author":"Shi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_38","first-page":"1","article-title":"KATP Channel Action in Vascular Tone Regulation: From Genetics to Diseases","volume":"64","author":"Shi","year":"2012","journal-title":"Sheng Li Xue Bao"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1161\/01.RES.0000128513.34817.c4","article-title":"Multisite Phosphorylation Mechanism for Protein Kinase A Activation of the Smooth Muscle ATP-Sensitive K+ Channel","volume":"94","author":"Quinn","year":"2004","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7523","DOI":"10.1074\/jbc.M709941200","article-title":"CAMP-Dependent Protein Kinase Phosphorylation Produces Interdomain Movement in SUR2B Leading to Activation of the Vascular KATP Channel","volume":"283","author":"Shi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11916-020-00911-6","article-title":"Latest Insights into the Pathophysiology of Migraine: The ATP-Sensitive Potassium Channels","volume":"24","author":"Kokoti","year":"2020","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/WCO.0b013e328337b884","article-title":"What Have We Learnt from Triggering Migraine?","volume":"23","author":"Schytz","year":"2010","journal-title":"Curr. Opin. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1113\/jphysiol.1997.sp021963","article-title":"Sulphonylurea Receptor 2B and Kir6.1 Form a Sulphonylurea-Sensitive but ATP-Insensitive K+ Channel","volume":"499","author":"Yamada","year":"1997","journal-title":"J. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1152\/ajprenal.90440.2008","article-title":"ATP-Sensitive K+ Channels in Pig Urethral Smooth Muscle Cells Are Heteromultimers of Kir6.1 and Kir6.2","volume":"296","author":"Teramoto","year":"2009","journal-title":"Am. J. Physiol Ren. Physiol"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1177\/03331024211053570","article-title":"Smooth Muscle ATP-Sensitive Potassium Channels Mediate Migraine-Relevant Hypersensitivity in Mouse Models","volume":"42","author":"Christensen","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s10194-017-0800-8","article-title":"The KATP Channel in Migraine Pathophysiology: A Novel Therapeutic Target for Migraine","volume":"18","author":"Hansen","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1177\/0333102420925513","article-title":"ATP Sensitive Potassium (KATP) Channel Inhibition: A Promising New Drug Target for Migraine","volume":"40","author":"Christensen","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/164_2021_466","article-title":"The Pharmacology of ATP-Sensitive K + Channels (K ATP)","volume":"267","author":"Li","year":"2021","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/glia.10073","article-title":"Functional Expression of Kir 6.1\/SUR1-KATP Channels in Frog Retinal M\u00fcller Glial Cells","volume":"38","author":"Skatchkov","year":"2002","journal-title":"Glia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejphar.2008.10.041","article-title":"KATP Channels in Pig and Human Intracranial Arteries","volume":"601","author":"Ploug","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/19336950.2015.1004289","article-title":"ATP-Sensitive Potassium Channels and Vascular Function","volume":"9","author":"Aziz","year":"2015","journal-title":"Channels"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ejphar.2010.03.027","article-title":"Presence and Vascular Pharmacology of KATP Channel Subtypes in Rat Central and Peripheral Tissues","volume":"637","author":"Ploug","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2174\/1381612054021015","article-title":"ATP-Sensitive Potassium Channels","volume":"11","author":"Rodrigo","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1161\/CIRCEP.111.964643","article-title":"Unique Properties of the ATP-Sensitive K+ Channel in the Mouse Ventricular Cardiac Conduction System","volume":"4","author":"Bao","year":"2011","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1126\/science.7716547","article-title":"Cloning of the Beta Cell High-Affinity Sulfonylurea Receptor: A Regulator of Insulin Secretion","volume":"268","author":"Nichols","year":"1995","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1161\/CIRCRESAHA.108.178186","article-title":"Differential Structure of Atrial and Ventricular KATP: Atrial KATP Channels Require SUR1","volume":"103","author":"Flagg","year":"2008","journal-title":"Circ. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zoga, V., Kawano, T., Liang, M.Y., Bienengraeber, M., Weihrauch, D., McCallum, B., Gemes, G., Hogan, Q., and Sarantopoulos, C. (2010). KATPchannel Subunits in Rat Dorsal Root Ganglia: Alterations by Painful Axotomy. Mol. Pain, 6.","DOI":"10.1186\/1744-8069-6-6"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.neuroscience.2009.04.076","article-title":"ATP-Sensitive Potassium Currents in Rat Primary Afferent Neurons: Biophysical, Pharmacological Properties, and Alterations by Painful Nerve Injury","volume":"162","author":"Kawano","year":"2009","journal-title":"Neuroscience"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1073\/pnas.0505974103","article-title":"Hybrid Assemblies of ATP-Sensitive K+ Channels Determine Their Muscle-Type-Dependent Biophysical and Pharmacological Properties","volume":"103","author":"Tricarico","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0896-6273(00)80124-5","article-title":"A Family of Sulfonylurea Receptors Determines the Pharmacological Properties of ATP-Sensitive K+ Channels","volume":"16","author":"Inagaki","year":"1996","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.neuroscience.2006.10.043","article-title":"Kir6.2-Containing ATP-Sensitive Potassium Channels Protect Cortical Neurons from Ischemic\/Anoxic Injury in Vitro and in Vivo","volume":"144","author":"Sun","year":"2007","journal-title":"Neuroscience"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.biocel.2015.10.029","article-title":"Phenylephrine Preconditioning in Embryonic Heart H9c2 Cells Is Mediated by Up-Regulation of SUR2B\/Kir6.2: A First Evidence for Functional Role of SUR2B in Sarcolemmal KATP Channels and Cardioprotection","volume":"70","author":"Ballantyne","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yjmcc.2005.04.006","article-title":"K(ATP) Channel Therapeutics at the Bedside","volume":"39","author":"Jahangir","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1161\/HYPERTENSIONAHA.114.03116","article-title":"The ATP-Sensitive Potassium Channel Subunit, Kir6.1, in Vascular Smooth Muscle Plays a Major Role in Blood Pressure Control","volume":"64","author":"Aziz","year":"2014","journal-title":"Hypertension"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1111\/j.1526-4610.2008.01205.x","article-title":"Role of KATP Channels in Cephalic Vasodilatation Induced by Calcitonin Gene-Related Peptide, Nitric Oxide, and Transcranial Electrical Stimulation in the Rat","volume":"48","author":"Gozalov","year":"2008","journal-title":"Headache"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1152\/ajpcell.1995.268.4.C799","article-title":"Physiological Roles and Properties of Potassium Channels in Arterial Smooth Muscle","volume":"268","author":"Nelson","year":"1995","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/bph.12407","article-title":"The Role of ATP-Sensitive Potassium Channels in Cellular Function and Protection in the Cardiovascular System","volume":"171","author":"Tinker","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1113\/jphysiol.1995.sp020789","article-title":"Nitric Oxide Hyperpolarizes Rabbit Mesenteric Arteries via ATP-Sensitive Potassium Channels","volume":"486","author":"Murphy","year":"1995","journal-title":"J. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pharmthera.2008.08.003","article-title":"The Role of Nitric Oxide (NO) in Migraine, Tension-Type Headache and Cluster Headache","volume":"120","author":"Olesen","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0014-2999(92)90881-4","article-title":"Analgesia by Direct Antagonism of Nociceptor Sensitization Involves the Arginine-Nitric Oxide-CGMP Pathway","volume":"217","author":"Duarte","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17587","DOI":"10.1074\/jbc.M117.810325","article-title":"Molecular and Functional Characterization of the Endothelial ATP-Sensitive Potassium Channel","volume":"292","author":"Aziz","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s10194-019-0968-1","article-title":"Migraine-Provoking Substances Evoke Periorbital Allodynia in Mice","volume":"20","author":"Landini","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.nurt.2010.02.003","article-title":"The PACAP Receptor: A Novel Target for Migraine Treatment","volume":"7","author":"Schytz","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Brown, T., Forster, R.B., Cleanthis, M., Mikhailidis, D.P., Stansby, G., and Stewart, M. (2021). Cilostazol for Intermittent Claudication. Cochrane Database Syst. Rev., 2021.","DOI":"10.1002\/14651858.CD003748.pub5"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2490-2-6","article-title":"Sildenafil (Viagra) for Male Erectile Dysfunction: A Meta-Analysis of Clinical Trial Reports","volume":"2","author":"Moore","year":"2002","journal-title":"BMC Urol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/00039896.1966.10664362","article-title":"Headaches in Explosive Magazine Workers","volume":"12","author":"Trainor","year":"1966","journal-title":"Arch. Environ. Health"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nm0502-466","article-title":"Mouse Model of Prinzmetal Angina by Disruption of the Inward Rectifier Kir6.1","volume":"8","author":"Miki","year":"2002","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0168-9525(97)01326-7","article-title":"Controlling Your Losses: Conditional Gene Silencing in Mammals","volume":"14","author":"Porter","year":"1998","journal-title":"Trends Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1006\/meth.1998.0593","article-title":"Inducible Gene Targeting in Mice Using the Cre\/Lox System","volume":"14","author":"Sauer","year":"1998","journal-title":"Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/15073","article-title":"Temporal, Spatial, and Cell Type-Specified Control of Cre-Mediated DNA Recombination in Transgenic Mice","volume":"17","author":"Utomo","year":"1999","journal-title":"Nat. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1111\/j.1471-4159.2007.04963.x","article-title":"Role of K ATP Channels in Protection against Neuronal Excitatory Insults","volume":"103","author":"Soundarapandian","year":"2007","journal-title":"J. Neurochem"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.brainresbull.2021.02.009","article-title":"KATP and TRPM2-like Channels Couple Metabolic Status to Resting Membrane Potential of Octopus Neurons in the Mouse Ventral Cochlear Nucleus","volume":"170","author":"Yildirim","year":"2021","journal-title":"Brain Res. Bull."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/619747","article-title":"The Role of HCN Channels on Membrane Excitability in the Nervous System","volume":"2012","author":"Kase","year":"2012","journal-title":"J. Signal. Transduct."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Country, M.W., and Jonz, M.G. (2021). Mitochondrial KATP Channels Stabilize Intracellular Ca2+ during Hypoxia in Retinal Horizontal Cells of Goldfish (Carassius Auratus). J. Exp. Biol., 224.","DOI":"10.1242\/jeb.242634"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Guo, W., Tang, Z.Y., Cai, Z.Y., Zhao, W.E., Yang, J., Wang, X.P., Ji, J., Huang, X.X., and Sun, X.L. (2021). Iptakalim Alleviates Synaptic Damages via Targeting Mitochondrial ATP-Sensitive Potassium Channel in Depression. FASEB J., 35.","DOI":"10.1096\/fj.202100124RR"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1471-4159.2010.06785.x","article-title":"KATP Channel Blockade Protects Midbrain Dopamine Neurons by Repressing a Glia-to-Neuron Signaling Cascade That Ultimately Disrupts Mitochondrial Calcium Homeostasis","volume":"114","author":"Toulorge","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1472-8206.2010.00880.x","article-title":"Interaction of Morphine and Potassium Channel Openers on Experimental Models of Pain in Mice","volume":"25","author":"Khanna","year":"2011","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.tins.2013.12.002","article-title":"Opening Paths to Novel Analgesics: The Role of Potassium Channels in Chronic Pain","volume":"37","author":"Tsantoulas","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1073\/pnas.0914733107","article-title":"Morphine Peripheral Analgesia Depends on Activation of the PI3K\u03b3\/AKT\/NNOS\/NO\/KATP Signaling Pathway","volume":"107","author":"Cunha","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"146567","DOI":"10.1016\/j.brainres.2019.146567","article-title":"Choline Attenuates Inflammatory Hyperalgesia Activating Nitric Oxide\/CGMP\/ATP-Sensitive Potassium Channels Pathway","volume":"1727","author":"Kusuda","year":"2020","journal-title":"Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1097\/FBP.0000000000000579","article-title":"The Antinociceptive Mechanisms of Melatonin: Role of L-Arginine\/Nitric Oxide\/Cyclic GMP\/KATP Channel Signaling Pathway","volume":"31","author":"Fakhri","year":"2020","journal-title":"Behav. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.neuroscience.2014.12.058","article-title":"Oxytocin-Induced Membrane Hyperpolarization in Pain-Sensitive Dorsal Root Ganglia Neurons Mediated by Ca(2+)\/NNOS\/NO\/KATP Pathway","volume":"289","author":"Gong","year":"2015","journal-title":"Neuroscience"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0304-3940(03)00383-5","article-title":"ATP-Sensitive Potassium Channels in Rat Primary Afferent Neurons: The Effect of Neuropathic Injury and Gabapentin","volume":"343","author":"Sarantopoulos","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1016\/j.pain.2011.08.003","article-title":"Reopening of ATP-Sensitive Potassium Channels Reduces Neuropathic Pain and Regulates Astroglial Gap Junctions in the Rat Spinal Cord","volume":"152","author":"Wu","year":"2011","journal-title":"Pain"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sakamaki, G., Johnson, K., Mensinger, M., Hmu, E., and Klein, A.H. (2021). Loss of SUR1 Subtype KATP Channels Alters Antinociception and Locomotor Activity after Opioid Administration. Behav. Brain Res., 414.","DOI":"10.1016\/j.bbr.2021.113467"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Fisher, C., Johnson, K., Okerman, T., Jurgenson, T., Nickell, A., Salo, E., Moore, M., Doucette, A., Bjork, J., and Klein, A.H. (2019). Morphine Efficacy, Tolerance, and Hypersensitivity Are Altered After Modulation of SUR1 Subtype KATP Channel Activity in Mice. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01122"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1074\/jbc.M109.058313","article-title":"Lipopolysaccharides Up-Regulate Kir6.1\/SUR2B Channel Expression and Enhance Vascular KATP Channel Activity via NF-KappaB-Dependent Signaling","volume":"285","author":"Shi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1097\/AJP.0000000000000299","article-title":"Opening of the Adenosine Triphosphate-Sensitive Potassium Channel Attenuates Morphine Tolerance by Inhibiting JNK and Astrocyte Activation in the Spinal Cord","volume":"32","author":"Cao","year":"2016","journal-title":"Clin. J. Pain"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1177\/03331024211038884","article-title":"CGRP-Dependent Signalling Pathways Involved in Mouse Models of GTN- Cilostazol- and Levcromakalim-Induced Migraine","volume":"41","author":"Christensen","year":"2021","journal-title":"Cephalalgia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0006-8993(92)91549-T","article-title":"Role of Central ATP-Sensitive Potassium Channels in the Analgesic Effect and Spinal Noradrenaline Turnover-Enhancing Effect of Intracerebroventricularly Injected Morphine in Mice","volume":"596","author":"Narita","year":"1992","journal-title":"Brain Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1053\/j.sempedsurg.2010.10.012","article-title":"KATP Channel Mutations in Congenital Hyperinsulinism","volume":"20","author":"Arnoux","year":"2011","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/humu.23995","article-title":"Update of Variants Identified in the Pancreatic \u03b2-Cell KATP Channel Genes KCNJ11 and ABCC8 in Individuals with Congenital Hyperinsulinism and Diabetes","volume":"41","author":"Brusgaard","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/nm1296-1344","article-title":"Loss of Functional KATP Channels in Pancreatic Beta-Cells Causes Persistent Hyperinsulinemic Hypoglycemia of Infancy","volume":"2","author":"Kane","year":"1996","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2337\/db17-0029","article-title":"Functional and Metabolomic Consequences of K ATP Channel Inactivation in Human Islets","volume":"66","author":"Li","year":"2017","journal-title":"Diabetes"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s11892-013-0375-y","article-title":"Diabetes Mellitus and Inflammation","volume":"13","author":"Sobngwi","year":"2013","journal-title":"Curr. Diab. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1089\/dia.2006.8.7","article-title":"The Epidemiology of Low-Grade Chronic Systemic Inflammation and Type 2 Diabetes","volume":"8","author":"Duncan","year":"2006","journal-title":"Diabetes Technol. Ther."},{"key":"ref_107","first-page":"3246","article-title":"Suppression of KATP Channel Activity Protects Murine Pancreatic Beta Cells against Oxidative Stress","volume":"119","author":"Gier","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1007\/BF00378534","article-title":"H2O2 Induced Hyperpolarization of Pancreatic B-Cells","volume":"426","author":"Lang","year":"1994","journal-title":"Pflug. Arch."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"27905","DOI":"10.1074\/jbc.274.39.27905","article-title":"Hydrogen Peroxide Alters Mitochondrial Activation and Insulin Secretion in Pancreatic Beta Cells","volume":"274","author":"Maechler","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"878","DOI":"10.2337\/diab.44.8.878","article-title":"Involvement of ATP-Sensitive K+ Channels in Free Radical-Mediated Inhibition of Insulin Secretion in Rat Pancreatic Beta-Cells","volume":"44","author":"Nakazaki","year":"1995","journal-title":"Diabetes"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1007\/s00125-015-3577-9","article-title":"Mitochondrial Succinate Dehydrogenase Is Involved in Stimulus-Secretion Coupling and Endogenous ROS Formation in Murine Beta Cells","volume":"58","author":"Edalat","year":"2015","journal-title":"Diabetologia"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1111\/bph.12512","article-title":"The TRPA1 Channel in Migraine Mechanism and Treatment","volume":"171","author":"Benemei","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1177\/03331024211017884","article-title":"Targeting Reactive Nitroxidative Species in Preclinical Models of Migraine","volume":"41","author":"Akerman","year":"2021","journal-title":"Cephalalgia"},{"key":"ref_114","first-page":"832","article-title":"ATP-Sensitive K+ Channel Modulator Binding to Sulfonylurea Receptors SUR2A and SUR2B: Opposite Effects of MgADP","volume":"55","author":"Hambrock","year":"1999","journal-title":"Mol. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s002100000270","article-title":"Vasodilator Effects of KRN2391, Levcromakalim and 3-Morpholino- Sydnonimin in Human Pial and Omental Arteries","volume":"362","author":"Petersson","year":"2000","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ejphar.2005.08.028","article-title":"Characterization of KATP-Channels in Rat Basilar and Middle Cerebral Arteries: Studies of Vasomotor Responses and MRNA Expression","volume":"523","author":"Mortensen","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/bjp.2008.86","article-title":"KATP Channel Expression and Pharmacological in Vivo and in Vitro Studies of the KATP Channel Blocker PNU-37883A in Rat Middle Meningeal Arteries","volume":"154","author":"Ploug","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/BF00542128","article-title":"Pinacidil, a New Vasodilator: Pharmacokinetics and Pharmacodynamics of a New Retarded Release Tablet in Essential Hypertension","volume":"25","author":"Carlsen","year":"1983","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/BF00543493","article-title":"Pharmacokinetics and Hypotensive Effect in Healthy Volunteers of Pinacidil, a New Potent Vasodilator","volume":"26","author":"Ward","year":"1984","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0014-2999(94)90697-1","article-title":"K+ Channel Activators, Acute Glucose Tolerance and Glibenclamide-Induced Hypoglycaemia in the Hypertensive Rat","volume":"257","author":"Clapham","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/med.10060","article-title":"KATP Channel Openers: Structure-Activity Relationships and Therapeutic Potential","volume":"24","author":"Mannhold","year":"2004","journal-title":"Med. Res. Rev."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0140-6736(64)92414-6","article-title":"Diazoxide Hyperglycaemia and Its Continued Relief by Tolbutamide","volume":"1","author":"Wolff","year":"1964","journal-title":"Lancet"},{"key":"ref_123","first-page":"344","article-title":"Pharmacology of Diazoxide, an Antihypertensive, Nondiuretic Benzothiadiazine","volume":"136","author":"Rubin","year":"1962","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/BJ20140273","article-title":"Sulfonylurea Receptors Regulate the Channel Pore in ATP-Sensitive Potassium Channels via an Intersubunit Salt Bridge","volume":"464","author":"Lodwick","year":"2014","journal-title":"Biochem. J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"740","DOI":"10.7326\/M15-2650","article-title":"Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-Analysis","volume":"164","author":"Maruthur","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1021\/jm000484+","article-title":"Recent Developments in the Biology and Medicinal Chemistry of Potassium Channel Modulators: Update from a Decade of Progress","volume":"44","author":"Coghlan","year":"2001","journal-title":"J. Med. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.2337\/diabetes.47.9.1412","article-title":"Tissue Specificity of Sulfonylureas Studies on Cloned Cardiac and \u03b2- Cell K(ATP) Channels","volume":"47","author":"Gribble","year":"1998","journal-title":"Diabetes"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.diabres.2015.05.036","article-title":"The Effect of Gliquidone on KATP Channels in Pancreatic \u03b2-Cells, Cardiomyocytes, and Vascular Smooth Muscle Cells","volume":"109","author":"Liu","year":"2015","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_129","unstructured":"(2022, June 26). Glibenclamide|Ligand Activity Charts|IUPHAR\/BPS Guide to PHARMACOLOGY. Available online: https:\/\/www.guidetopharmacology.org\/GRAC\/LigandActivityRangeVisForward?ligandId=2414."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.bcp.2013.02.039","article-title":"Differential Sensitivities of the Vascular K(ATP) Channel to Various PPAR Activators","volume":"85","author":"Wang","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1476-5381.2012.01934.x","article-title":"Rosiglitazone Selectively Inhibits KATP Channels by Acting on the KIR6 Subunit","volume":"167","author":"Yu","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1527-3466.1999.tb00022.x","article-title":"Pharmacology of the K-ATP Channel Blocking Morpholinoguanidine PNU- 37883A","volume":"17","author":"Humphrey","year":"1999","journal-title":"Cardiovasc. Drug Rev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/BF00543335","article-title":"Pinacidil, a New Vasodilator, in the Treatment of Mild to Moderate Essential Hypertension","volume":"28","author":"Laher","year":"1985","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1136\/thx.48.2.130","article-title":"Effect of an Oral Potassium Channel Activator, BRL 38227, on Airway Function and Responsiveness in Asthmatic Patients: Comparison with Oral Salbutamol","volume":"48","author":"Kidney","year":"1993","journal-title":"Thorax"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1177\/0333102412475234","article-title":"Pearls and Pitfalls in Human Pharmacological Models of Migraine: 30 Years\u2019 Experience","volume":"33","author":"Ashina","year":"2013","journal-title":"Cephalalgia"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1111\/head.13634","article-title":"Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but Not Cerebral Arteries","volume":"59","author":"Ghanizada","year":"2019","journal-title":"Headache"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1177\/0271678X20959294","article-title":"Cerebrovascular Effects of Glibenclamide Investigated Using High-Resolution Magnetic Resonance Imaging in Healthy Volunteers","volume":"41","author":"Ghanizada","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1468-2982.2004.00848.x","article-title":"Role of KATP Channels in the Regulation of Rat Dura and Pia Artery Diameter","volume":"25","author":"Gozalov","year":"2005","journal-title":"Cephalalgia"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.ejphar.2006.09.053","article-title":"Pharmacological and Molecular Comparison of KATP Channels in Rat Basilar and Middle Cerebral Arteries","volume":"553","author":"Ploug","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Rasmussen, R.H., Jansen-Olesen, I., Kristensen, D.M., and Christensen, S.L. (2022). Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents|Protocol. J. Vis. Exp., 183.","DOI":"10.3791\/63723-v"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/0333102411430266","article-title":"K ATP Channel Openers in the Trigeminovascular System","volume":"32","author":"Ploug","year":"2012","journal-title":"Cephalalgia"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin Gene-Related Peptide: Physiology and Pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1526-4610.1963.hed0303086.x","article-title":"Mast cells and their active substances: Their role in the pathogenesis of migraine","volume":"3","author":"Sicuteri","year":"1963","journal-title":"Headache"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/j.1468-2982.2009.01864.x","article-title":"Sumatriptan Alleviates Nitroglycerin-Induced Mechanical and Thermal Allodynia in Mice","volume":"30","author":"Bates","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.pain.2013.10.004","article-title":"Characterization of a Novel Model of Chronic Migraine","volume":"155","author":"Pradhan","year":"2014","journal-title":"PAIN\u00ae"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1093\/brain\/awac040","article-title":"The PACAP Pathway Is Independent of CGRP in Mouse Models of Migraine: Possible New Drug Target?","volume":"145","author":"Ernstsen","year":"2022","journal-title":"Brain"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000159197","article-title":"Pituitary Adenylate-Cyclase-Activating Peptides Relax Human Coronary Arteries by Activating K(ATP) and K(Ca) Channels in Smooth Muscle Cells","volume":"34","author":"Bruch","year":"1997","journal-title":"J. Vasc. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1469-7793.2001.0193l.x","article-title":"Angiotensin II Inhibits Rat Arterial KATP Channels by Inhibiting Steady-State Protein Kinase A Activity and Activating Protein Kinase C\u03b5","volume":"530","author":"Hayabuchi","year":"2001","journal-title":"J. Physiol."},{"key":"ref_149","first-page":"655","article-title":"4-Morpholinecarboximidine-N-1-Adamantyl-N\u2019-Cyclohexylhydrochloride (U- 37883A): Pharmacological Characterization of a Novel Antagonist of Vascular ATP-Sensitive K+ Channel Openers","volume":"266","author":"Meisheri","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/00004647-199701000-00013","article-title":"Role of Nitric Oxide, Cyclic Nucleotides, and the Activation of ATP-Sensitive K+ Channels in the Contribution of Adenosine to Hypoxia-Induced Pial Artery Dilation","volume":"17","author":"Armstead","year":"1997","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1111\/j.1526-4610.2012.02247.x","article-title":"Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache","volume":"52","author":"Oshinsky","year":"2012","journal-title":"Headache"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1038\/s41598-018-19901-1","article-title":"A Unique Inbred Rat Strain with Sustained Cephalic Hypersensitivity as a Model of Chronic Migraine-like Pain","volume":"8","author":"Munro","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0333102420949863","article-title":"Effect of KATP Channel Blocker Glibenclamide on Levcromakalim-Induced Headache","volume":"40","author":"Ghanizada","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"652136","DOI":"10.3389\/fphys.2021.652136","article-title":"The Effect of KATP Channel Blocker Glibenclamide on CGRP-Induced Headache and Hemodynamic in Healthy Volunteers","volume":"12","author":"Coskun","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1177\/03331024221080574","article-title":"Effect of KATP Channel Blocker Glibenclamide on PACAP38-Induced Headache and Hemodynamic","volume":"42","author":"Kokoti","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_156","unstructured":"(2022, June 27). Home\u2014ClinicalTrials.Gov, Available online: https:\/\/www.clinicaltrials.gov\/."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose Translation from Animal to Human Studies Revisited","volume":"22","author":"Nihal","year":"2008","journal-title":"FASEB J."},{"key":"ref_159","first-page":"562","article-title":"The Route of Absorption of Intraperitoneally Administered Compounds","volume":"178","author":"Lukas","year":"1971","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Remedi, M.S., and Nichols, C.G. (2008). Chronic Antidiabetic Sulfonylureas In Vivo: Reversible Effects on Mouse Pancreatic \u03b2-Cells. PLoS Med., 5.","DOI":"10.1371\/journal.pmed.0050206"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0134476","article-title":"Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents","volume":"10","author":"Lahmann","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s001250051247","article-title":"ATP-Sensitive K+ Channels and Insulin Secretion: Their Role in Health and Disease","volume":"42","author":"Ashcroft","year":"1999","journal-title":"Diabetologia"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/sj.bjp.0703936","article-title":"Mechanism of CGRP-Induced Relaxation in Rat Intramural Coronary Arteries","volume":"132","author":"Sheykhzade","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1093\/brain\/awaa003","article-title":"Hyperpolarization through ATP-Sensitive Potassium Channels; Relevance to Migraine Pathology","volume":"143","author":"Haanes","year":"2020","journal-title":"Brain"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.1093\/brain\/awaa004","article-title":"Reply: Hyperpolarization through ATP-Sensitive Potassium Channels; Relevance to Migraine Pathology","volume":"143","author":"Olesen","year":"2020","journal-title":"Brain"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Tsantoulas, C., Lainez, S., Wong, S., Mehta, I., Vilar, B., and McNaughton, P.A. (2017). Hyperpolarization-Activated Cyclic Nucleotide-Gated 2 (HCN2) Ion Channels Drive Pain in Mouse Models of Diabetic Neuropathy. Sci. Transl. Med., 9.","DOI":"10.1126\/scitranslmed.aam6072"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e967","DOI":"10.1097\/PR9.0000000000000967","article-title":"Role of Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion Channels in Neuropathic Pain: A Proof-of-Concept Study of Ivabradine in Patients with Chronic Peripheral Neuropathic Pain","volume":"6","author":"Scholtes","year":"2021","journal-title":"Pain Rep."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1016\/j.pain.2014.05.021","article-title":"Inflammatory and Neuropathic Pain Are Rapidly Suppressed by Peripheral Block of Hyperpolarisation-Activated Cyclic Nucleotide-Gated Ion Channels","volume":"155","author":"Young","year":"2014","journal-title":"Pain"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1002\/jnr.20109","article-title":"Hyperpolarization-Activated, Cyclic Nucleotide-Gated Cation Channels: Roles in the Differential Electrophysiological Properties of Rat Primary Afferent Neurons","volume":"76","author":"Tu","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"5911","DOI":"10.1113\/jphysiol.2008.163154","article-title":"Role of the Hyperpolarization-Activated Current Ih in Somatosensory Neurons","volume":"586","author":"Momin","year":"2008","journal-title":"J. Physiol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1177\/0333102419888490","article-title":"Extracranial Activation of ATP-Sensitive Potassium Channels Induces Vasodilation without Nociceptive Effects","volume":"39","author":"Ghanizada","year":"2019","journal-title":"Cephalalgia"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Zhang, J., Yao, J., and Rong, M. (2022). Editorial: Role of Ion Channels in Pain. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.884665"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1021\/jm00048a005","article-title":"Synthesis and Diuretic Activity of Alkyl- and Arylguanidine Analogs of N,N\u2019-Dicyclohexyl-4-Morpholinecarboxamidine in Rats and Dogs","volume":"37","author":"Perricone","year":"1994","journal-title":"J. Med. Chem."},{"key":"ref_174","first-page":"247","article-title":"Cardiovascular Effects of the K-ATP Channel Blocker U-37883A and Structurally Related Morpholinoguanidines","volume":"18","author":"Humphrey","year":"1996","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1172\/JCI0215672","article-title":"Episodic Coronary Artery Vasospasm and Hypertension Develop in the Absence of Sur2 K(ATP) Channels","volume":"110","author":"Chutkow","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1161\/01.RES.0000207498.40005.e7","article-title":"Spontaneous Coronary Vasospasm in KATP Mutant Mice Arises from a Smooth Muscle-Extrinsic Process","volume":"98","author":"Kakkar","year":"2006","journal-title":"Circ. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jmb.2014.07.027","article-title":"From Foe to Friend: Using Animal Toxins to Investigate Ion Channel Function","volume":"427","author":"Kalia","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/19420862.2018.1548232","article-title":"Ion Channels as Therapeutic Antibody Targets","volume":"11","author":"Hutchings","year":"2019","journal-title":"MAbs"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1152\/ajpheart.00421.2003","article-title":"KATP Channels and Myocardial Preconditioning: An Update","volume":"285","author":"Gross","year":"2003","journal-title":"Am. J. Physiol. Hear. Circ. Physiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1161\/01.CIR.85.4.1627","article-title":"Role of K+ Channel Activators in Cardiac Electrophysiology and Arrhythmias","volume":"85","author":"Antzelevitch","year":"1992","journal-title":"Circulation"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"King, D.R., Hardin, K.M., Hoeker, G.S., and Poelzing, S. (2022). Re-Evaluating Methods Reporting Practices to Improve Reproducibility: An Analysis of Methodological Rigor for the Langendorff Whole-Heart Technique. Am. J. Physiol. Circ. Physiol.","DOI":"10.1152\/ajpheart.00164.2022"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/15\/2406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:04:05Z","timestamp":1760141045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/15\/2406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,4]]},"references-count":181,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cells11152406"],"URL":"https:\/\/doi.org\/10.3390\/cells11152406","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,4]]}}}