{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:15:09Z","timestamp":1768900509635,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"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":[[2002,10]]},"abstract":"<jats:p>Regulation of the ryanodine receptor (RYR) by Mg<jats:sup>2+<\/jats:sup> and SR luminal Ca<jats:sup>2+<\/jats:sup> was studied in mechanically skinned malignant hyperthermia susceptible (MHS) and non\u2010susceptible (MHN) fibres from human vastus medialis. Preparations were perfused with solutions mimicking the intracellular milieu and changes in [Ca<jats:sup>2+<\/jats:sup>] were detected using fura\u20102 fluorescence. At 1 m<jats:sc>m<\/jats:sc> cytosolic Mg<jats:sup>2+<\/jats:sup>, MHS fibres had a higher sensitivity to caffeine (2\u201040 m<jats:sc>m<\/jats:sc>) than MHN fibres. The inhibitory effect of Mg<jats:sup>2+<\/jats:sup> on caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> release was studied by increasing [Mg<jats:sup>2+<\/jats:sup>] of the solution containing 40 m<jats:sc>m<\/jats:sc> caffeine. Increasing [Mg<jats:sup>2+<\/jats:sup>] from 1 to 3 m<jats:sc>m<\/jats:sc> reduced the amplitude of the caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> transient by 77 \u00b1 7.4 % (<jats:italic>n<\/jats:italic>= 8) in MHN fibres. However, the caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> transient decreased by only 24 \u00b1 8.1 % (<jats:italic>n<\/jats:italic>= 9) in MHS fibres. In MHN fibres, reducing the Ca<jats:sup>2+<\/jats:sup> loading period from 4 to 1 min (at 1 m<jats:sc>m<\/jats:sc> Mg<jats:sup>2+<\/jats:sup>) decreased the fraction of the total sarcoplasmic reticulum (SR) Ca<jats:sup>2+<\/jats:sup> content released in response to 40 m<jats:sc>m<\/jats:sc> caffeine by 90.4 \u00b1 6.2 % (<jats:italic>n<\/jats:italic>= 6). However, in MHS fibres the response was reduced by only 31.2 \u00b1 17.4 % (<jats:italic>n<\/jats:italic>= 6) under similar conditions. These results suggest that human malignant hyperthermia (MH) is associated with reduced inhibition of the RYR by (i) cytosolic Mg<jats:sup>2+<\/jats:sup> and (ii) SR Ca<jats:sup>2+<\/jats:sup> depletion. Both of these effects may contribute to increased sensitivity of the RYR to caffeine and volatile anaesthetics.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.022749","type":"journal-article","created":{"date-parts":[[2002,9,30]],"date-time":"2002-09-30T23:42:18Z","timestamp":1033429338000},"page":"85-95","source":"Crossref","is-referenced-by-count":18,"title":["Effects of Mg<sup>2+<\/sup> and SR luminal Ca<sup>2+<\/sup> on caffeine\u2010induced Ca<sup>2+<\/sup> release in skeletal muscle from humans susceptible to malignant hyperthermia"],"prefix":"10.1113","volume":"544","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 S.","family":"Steele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199301000-00023"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00203.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.11.2055"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.3.201"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.043by.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050610"},{"key":"e_1_2_5_8_1","first-page":"2P","article-title":"REACT: Calculation of free metal and ligand concentrations using a Windows\u2010based computer program","volume":"517","author":"Duncan L.","year":"1999","journal-title":"Journal of Physiology"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1977.57.1.71"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/56.11.1267"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp017916"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(91)90060-O"},{"key":"e_1_2_5_13_1","first-page":"763","article-title":"Malignant hyperthermia: halothane\u2010 and calcium\u2010induced calcium release in skeletal muscle","volume":"29","author":"Fletcher J. 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