{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T12:32:46Z","timestamp":1726057966246},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"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":[[2003,9]]},"abstract":"<jats:p>The effect of cytosolic Mg<jats:sup>2+<\/jats:sup> on halothane\u2010induced Ca<jats:sup>2+<\/jats:sup> release from the sarcoplasmic reticulum (SR) was investigated in mechanically skinned fibres from the rat extensor digitorum longus (EDL) muscle. Preparations were perfused with solutions mimicking the intracellular milieu and changes in [Ca<jats:sup>2+<\/jats:sup>] were detected using Fura\u20102 fluorescence. In the presence of 1 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup>, brief (500 ms) applications of 40 m<jats:sc>m<\/jats:sc> halothane failed to induce Ca<jats:sup>2+<\/jats:sup> release from the SR. However, Ca<jats:sup>2+<\/jats:sup> release became detectable when [Mg<jats:sup>2+<\/jats:sup>] was reduced to 0.4 m<jats:sc>m<\/jats:sc>, and the amplitude of the response increased progressively as [Mg<jats:sup>2+<\/jats:sup>] was further reduced to 0.2 and 0.1 m<jats:sc>m<\/jats:sc>. Lower halothane concentrations within the range found during anaesthesia or induction (0.1\u20131.2 m<jats:sc>m<\/jats:sc>) failed to induce SR Ca<jats:sup>2+<\/jats:sup> release at 0.2 or 0.4 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup>. However, in further experiments, preparations were exposed to 1 m<jats:sc>m<\/jats:sc> halothane for 2\u20103 min under conditions where the volume of solution surrounding the preparation was restricted by stopping the flow. In the absence of perfusion, 1 m<jats:sc>m<\/jats:sc> halothane induced Ca<jats:sup>2+<\/jats:sup> release from the SR at 0.4 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup> in two out of six preparations, and release was observed consistently at 0.2 and 0.1 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup>. Responses to 1 m<jats:sc>m<\/jats:sc> halothane induced in the presence of 0.4 and 0.2 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup> were typically delayed in onset and involved a localised release of Ca<jats:sup>2+<\/jats:sup> that propagated along the fibre. These results suggest that halothane\u2010induced Ca<jats:sup>2+<\/jats:sup> release is strongly inhibited at normal physiological levels of Mg<jats:sup>2+<\/jats:sup>. However, when Mg<jats:sup>2+<\/jats:sup>\u2010induced inhibition of the ryanodine receptor (RYR) is reduced, levels of halothane within the range found during anaesthesia can induce a marked efflux of Ca<jats:sup>2+<\/jats:sup> from the SR. This may be of relevance to the condition of malignant hyperthermia, where the inhibition of RYRs by Mg<jats:sup>2+<\/jats:sup> is reportedly reduced.<\/jats:p>","DOI":"10.1113\/jphysiol.2003.046623","type":"journal-article","created":{"date-parts":[[2003,8,30]],"date-time":"2003-08-30T01:50:26Z","timestamp":1062208226000},"page":"447-454","source":"Crossref","is-referenced-by-count":8,"title":["Mg<sup>2+<\/sup> dependence of halothane\u2010induced Ca<sup>2+<\/sup> release from the sarcoplasmic reticulum in rat skeletal muscle"],"prefix":"10.1113","volume":"551","author":[{"given":"Adrian M.","family":"Duke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip M.","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek 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