{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:51:06Z","timestamp":1793641866224,"version":"4.5.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2019,1,23]],"date-time":"2019-01-23T00:00:00Z","timestamp":1548201600000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT140101309"],"award-info":[{"award-number":["FT140101309"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1025355"],"award-info":[{"award-number":["APP1025355"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP180100937"],"award-info":[{"award-number":["DP180100937"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,8,7]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    In human muscle with ryanodine receptor (RyR) variants, there is expected to be a change in the basal RyRs Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak that may alter local Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics. It is not currently possible to assess these basal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics in human muscle. By trapping a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -sensitive fluorescent dye in the transverse tubular (t)-system of freshly biopsied human skeletal muscle fibers we could detect tiny local RyR-dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    movements. We show that malignant hyperthermia (MH) causative RyR variant human muscle displays a chronically different RyR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak which reconfigures the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -handling properties by the t-system. This approach can be used to assess human muscle for function and pathogenicity of other RyR variants of uncertain significance, MH susceptibility, and assessment of drugs targeted to the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -handling proteins.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1800490115","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T15:16:15Z","timestamp":1532358975000},"page":"8215-8220","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Junctional membrane Ca\n                    <sup>2+<\/sup>\n                    dynamics in human muscle fibers are altered by malignant hyperthermia causative RyR mutation"],"prefix":"10.1073","volume":"115","author":[{"given":"Tanya R.","family":"Cully","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky H.","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Bjorksten","sequence":"additional","affiliation":[{"name":"Malignant Hyperthermia Diagnostic Unit, Department of Anaesthesia and Pain Management, The Royal Melbourne Hospital, Melbourne, VIC 3050, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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