{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T23:32:20Z","timestamp":1767828740738,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cant\u00fa syndrome (CS) is caused by dominant gain\u2010of\u2010function mutation in ATP\u2010dependent potassium channels. Cellular ATP concentrations regulate potassium current thereby coupling energy status with membrane excitability. No specific pharmacotherapeutic options are available to treat CS but I<jats:sub>KATP<\/jats:sub> channels are pharmaceutical targets in type II diabetes or cardiac arrhythmia treatment. We have been suggested that I<jats:sub>KATP<\/jats:sub> inhibitors, glibenclamide and HMR1098, normalize CS channels. I<jats:sub>KATP<\/jats:sub> in response to Mg\u2010ATP, glibenclamide and HMR1098 were measured by inside\u2010out patch\u2010clamp electrophysiology. Results were interpreted in view of cryo\u2010EM I<jats:sub>KATP<\/jats:sub> channel structures. Mg\u2010ATP IC<jats:sub>50<\/jats:sub> values of outward current were increased for D207E (0.71\u00a0\u00b1\u00a00.14\u00a0mmol\/L), S1020P (1.83\u00a0\u00b1\u00a00.10), S1054Y (0.95\u00a0\u00b1\u00a00.06) and R1154Q (0.75\u00a0\u00b1\u00a00.13) channels compared to H60Y (0.14\u00a0\u00b1\u00a00.01) and wild\u2010type (0.15\u00a0\u00b1\u00a00.01). HMR1098 dose\u2010dependently inhibited S1020P and S1054Y channels in the presence of 0.15\u00a0mmol\/L Mg\u2010ATP, reaching, at 30\u00a0\u03bcmol\/L, current levels displayed by wild\u2010type and H60Y channels in the presence of 0.15\u00a0mmol\/L Mg\u2010ATP. Glibenclamide (10\u00a0\u03bcmol\/L) induced similar normalization. S1054Y sensitivity to glibenclamide increases strongly at 0.5\u00a0mmol\/L Mg\u2010ATP compared to 0.15\u00a0mmol\/L, in contrast to D207E and S1020P channels. Experimental findings agree with structural considerations. We conclude that CS channel activity can be normalized by existing drugs; however, complete normalization can be achieved at supraclinical concentrations only.<\/jats:p>","DOI":"10.1111\/jcmm.14329","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T14:25:32Z","timestamp":1558621532000},"page":"4962-4969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Glibenclamide and HMR1098 normalize Cant\u00fa syndrome\u2010associated gain\u2010of\u2010function currents"],"prefix":"10.1111","volume":"23","author":[{"given":"Marien J. 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