{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T17:40:41Z","timestamp":1775929241208,"version":"3.50.1"},"reference-count":0,"publisher":"Canadian Science Publishing","issue":"11","license":[{"start":{"date-parts":[[1986,11,1]],"date-time":"1986-11-01T00:00:00Z","timestamp":531187200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biochem. Cell Biol."],"published-print":{"date-parts":[[1986,11,1]]},"abstract":"<jats:p> Malignant hyperthermia is a muscle disease characterized by an abnormal response to anaesthetics, stress, and exercise. It is typified by muscle contracture and a dramatic elevation in body temperature. A defect in the regulation of the concentration of cytoplasmic free calcium, [Ca<jats:sup>2<\/jats:sup>]<jats:sub>i<\/jats:sub>, is thought to underlie this disease, but the actual [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was not measurable until recently. We have shown that the anaesthetic halothane increases [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in isolated lymphocytes from malignant hyperthermia-susceptible humans and pigs but not in the normal counterparts. In this report we extend these observations to a larger number of cases and analyze the molecular mechanisms responsible for the increase. The halothane-mediated rise in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> required external Ca<jats:sup>2+<\/jats:sup> and was prevented by nifedipine, an inhibitor of the voltage-sensitive Ca<jats:sup>2+<\/jats:sup> channels of the cell membrane. In addition, the effect of halothane on the releasable Ca<jats:sup>2+<\/jats:sup> from intracellular stores was determined by measuring the size of the releasable pool before and after addition of the anaesthetic. After addition of halothane, about 73% of this Ca<jats:sup>2+<\/jats:sup> pool was still available for release by the Ca<jats:sup>2+<\/jats:sup> ionophore ionomycin in cells from normal humans and pigs. In contrast, only about 45% of the free Ca<jats:sup>2+<\/jats:sup> in intracellular stores was left after treatment with halothane in cells from malignant hyperthermia-susceptible humans and swine. These results indicate that halothane acts both at the cell membrane and at intracellular organelles, and that this action results in a net increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in malignant hyperthermia, but not in normal cells. The action at the cell membrane appears to be on the voltage-sensitive Ca<jats:sup>2+<\/jats:sup> channels. Further, it is suggested that the halothane-mediated increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> could be used as the basis for a noninvasive test of malignant hyperthermia. <\/jats:p>","DOI":"10.1139\/o86-155","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T19:04:22Z","timestamp":1261595062000},"page":"1181-1189","source":"Crossref","is-referenced-by-count":19,"title":["Changes in cytoplasmic free calcium caused by halothane. Role of the plasma membrane and intracellular Ca<sup>2+<\/sup>stores"],"prefix":"10.1139","volume":"64","author":[{"given":"Amira","family":"Klip","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly A.","family":"Britt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Esther","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toolsie","family":"Ramlal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Pegg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","container-title":["Biochemistry and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdnsciencepub.com\/doi\/pdf\/10.1139\/o86-155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T18:05:20Z","timestamp":1751479520000},"score":1,"resource":{"primary":{"URL":"https:\/\/cdnsciencepub.com\/doi\/10.1139\/o86-155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1986,11,1]]},"references-count":0,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1986,11,1]]}},"alternative-id":["10.1139\/o86-155"],"URL":"https:\/\/doi.org\/10.1139\/o86-155","relation":{},"ISSN":["0829-8211","1208-6002"],"issn-type":[{"value":"0829-8211","type":"print"},{"value":"1208-6002","type":"electronic"}],"subject":[],"published":{"date-parts":[[1986,11,1]]}}}