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Fluorescence Ca\n                    <jats:sup>2+<\/jats:sup>\n                    imaging using the endoplasmic reticulum\u2013targeted fluorescent probes demonstrates that the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    burst originates from heat-induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release (HICR) through RyR1-mutant channels because of the channels\u2019 heat hypersensitivity. Furthermore, the variation in the heat hypersensitivity of four RyR1 mutants highlights the complexity of MH. HICR likewise occurs in skeletal muscles of MH model mice. We propose that HICR contributes an additional positive feedback to accelerate thermogenesis in patients with MH.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2201286119","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T13:26:53Z","timestamp":1659619613000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4090-025X","authenticated-orcid":false,"given":"Kotaro","family":"Oyama","sequence":"first","affiliation":[{"name":"Quantum Beam Science Research Directorate, National Institutes for Quantum Science and Technology, Takasaki-shi, Gunma 370-1292, Japan"},{"name":"PRESTO, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 332-0012, Japan"},{"name":"Department of Cell Physiology, The Jikei 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