{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T02:31:54Z","timestamp":1781577114237,"version":"3.54.5"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1989,6,1]],"date-time":"1989-06-01T00:00:00Z","timestamp":612662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1989,6]]},"abstract":"<jats:p>1. Twitch shortening of isolated rat ventricular myocytes was measured on exposure to complete metabolic blockade (2 mM\u2010cyanide in the presence of 10 mM\u20102\u2010deoxyglucose). Under these conditions twitch shortening declines to undetectable levels over 1\u201015 min. This \u2018early\u2019 contractile failure is followed by the development of a maintained contracture. 2. Contractures induced by caffeine (20 mM) were similar in amplitude before and after \u2018early\u2019 contractile failure. This result suggests that \u2018early\u2019 contractile failure is not due to depletion of Ca2+ from the sarcoplasmic reticulum. 3. The action potential shortened as the twitch magnitude declined during \u2018early\u2019 contractile failure, raising the possibility of a causal link. Voltage\u2010clamp experiments show that an enormous increase in K+ conductance (greater than 20\u2010fold) occurs during the period of \u2018early\u2019 contractile failure, and presumably underlies the action potential shortening. 4. If the K+ conductance changes are inhibited by replacement of intracellular K+ with N\u2010methyl glucosamine and inclusion of 2 mM\u2010tolbutamide in intra\u2010 and extracellular solutions, good voltage control can be achieved. Under these conditions, \u2018early\u2019 contractile failure did not occur on exposure to complete metabolic blockade and neither Ca2+ current nor the twitch were completely abolished until a maintained contracture had begun to occur. 5. Injection of ATP following \u2018early\u2019 contractile failure could partially restore the twitch and prolong the foreshortened action potential. 6. These results are consistent with the hypothesis that \u2018early\u2019 contractile failure occurring under non\u2010voltage\u2010clamped conditions is due principally to failure of activation of the Ca2+ current because of the shortening of the action potential. Although a decline in the availability of Ca2+ current also occurs, action potential shortening results mainly from increased conductance through ATP\u2010sensitive K+ channels which are activated by a fall of intracellular [ATP]. Contractile failure arises not because of a primary alteration, or defect, in the coupling of excitation to contraction, but because the cell membrane is effectively clamped at a potential close to the K+ equilibrium potential.<\/jats:p>","DOI":"10.1113\/jphysiol.1989.sp017657","type":"journal-article","created":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T02:01:18Z","timestamp":1418954478000},"page":"329-349","source":"Crossref","is-referenced-by-count":87,"title":["The mechanism of early contractile failure of isolated rat ventricular myocytes subjected to complete metabolic inhibition."],"prefix":"10.1113","volume":"413","author":[{"given":"W J","family":"Lederer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C G","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G L","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1989,6]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1989.sp017657","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1989.sp017657","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T15:29:17Z","timestamp":1697988557000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1989.sp017657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,6]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1989,6]]}},"alternative-id":["10.1113\/jphysiol.1989.sp017657"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1989.sp017657","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,6]]}}}