{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T12:02:45Z","timestamp":1779278565932,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":1796,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The opening of cardiac plasma\u2010membrane ATP\u2010sensitive K<jats:sup>+<\/jats:sup> channels (<jats:italic>pm<\/jats:italic>K<jats:sub>ATP<\/jats:sub>) can protect the heart against ischaemia\/reperfusion injury. We recently demonstrated that the resting membrane potential (<jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>) of ventricular myocytes strongly modulates reoxygenation\u2010induced Ca<jats:sup>2+<\/jats:sup> overload. This led to the hypothesis that activation of <jats:italic>pm<\/jats:italic>K<jats:sub>ATP<\/jats:sub> can influence the extent of chemically induced hypoxia (CIH)\/reoxygenation Ca<jats:sup>2+<\/jats:sup> overload <jats:italic>via<\/jats:italic> hyperpolarization of the diastolic membrane potential of ventricular myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The membrane potential (<jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub>) of isolated rat myocytes was determined using the perforated patch\u2010clamp technique and DiBac<jats:sub>4<\/jats:sub>(3) imaging. Intracellular Ca<jats:sup>2+<\/jats:sup> ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was monitored using FURA\u20102 imaging.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CIH\/reoxygenation caused a significant depolarization of <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> and a substantial increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The K<jats:sub>ATP<\/jats:sub> opener pinacidil (100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) and the <jats:italic>pm<\/jats:italic>K<jats:sub>ATP<\/jats:sub> opener P\u20101075 (100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) hyperpolarized the <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> of normoxic myocytes. Pinacidil (100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>) and P\u20101075 (10 and 100 <jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc>), applied during reoxygenation, hyperpolarized <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> and prevented reoxygenation\u2010induced increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Myocyte hypercontracture and death increased in parallel with an <jats:italic>E<\/jats:italic><jats:sub>m<\/jats:sub> depolarization of 10\u201315 mV and increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Under these conditions, the selective <jats:italic>pm<\/jats:italic>K<jats:sub>ATP<\/jats:sub> channel inhibitor HMR 1098 further depolarized myocyte membrane potential and increased hypercontracture.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, activation of <jats:italic>pm<\/jats:italic>K<jats:sub>ATP<\/jats:sub> channels can prevent CIH\/reoxygenation\u2010induced Ca<jats:sup>2+<\/jats:sup> overload <jats:italic>via<\/jats:italic> a mechanism that is dependent on hyperpolarization of diastolic membrane potential. Hyperpolarization toward normal resting membrane potential favours the Ca<jats:sup>2+<\/jats:sup> extrusion mode of Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchange.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>141<\/jats:bold>, 1059\u20131067. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705702\">10.1038\/sj.bjp.0705702<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705702","type":"journal-article","created":{"date-parts":[[2004,3,17]],"date-time":"2004-03-17T17:13:07Z","timestamp":1079543587000},"page":"1059-1067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Pharmacological activation of plasma\u2010membrane K<sub>ATP<\/sub> channels reduces reoxygenation\u2010induced Ca<sup>2+<\/sup> overload in cardiac myocytes <i>via<\/i> modulation of the diastolic membrane potential"],"prefix":"10.1111","volume":"141","author":[{"given":"Istv\u00e1n","family":"Baczk\u00f3","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne R","family":"Giles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter E","family":"Light","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.043372"},{"key":"e_1_2_8_3_1","first-page":"422a","article-title":"Activation of sarcolemmal KATP channels reduces hypoxia\/reoxygenation\u2010induced calcium overload via hyperpolarization of the resting membrane potential (abstract)","volume":"84","author":"BACZK\u00d3 I.","year":"2003","journal-title":"Biophys. 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