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The underlying mechanism of MH involves excessive Ca<jats:sup>2+<\/jats:sup> release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B\u2013lymphocytes, this study investigated whether cellular metabolism of native B\u2013lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4\u2013chloro\u2013m\u2013cresol (4-CmC) was used to challenge native B-lymphocytes in a real\u2013time, metabolic assay based on a pH\u2013sensitive silicon biosensor chip. At the cellular level, a dose\u2013dependent, phasic acidification occurred with 4\u2013CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B\u2013lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4\u2013CmC to evoke similar acidification rates to MHN. Native B\u2013lymphocytes from MHS individuals are more sensitive to 4\u2013CmC than those from MHN, reflecting a greater Ca<jats:sup>2+<\/jats:sup> turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B\u2013lymphocytes.<\/jats:p>","DOI":"10.1038\/srep33372","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T09:12:15Z","timestamp":1474362735000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hypermetabolism in B\u2013lymphocytes from malignant hyperthermia susceptible individuals"],"prefix":"10.1038","volume":"6","author":[{"given":"Kerstin","family":"Hoppe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Hack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lehmann\u2013Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Jurkat\u2013Rott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Carsana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Klingler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"BFsrep33372_CR1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/bja\/aer132","volume":"107","author":"PM Hopkins","year":"2011","unstructured":"Hopkins, P. 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