{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:40:34Z","timestamp":1792618834686,"version":"4.5.0"},"reference-count":27,"publisher":"MyJove Corporation","issue":"172","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoVE"],"DOI":"10.3791\/62196","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T20:01:30Z","timestamp":1623268890000},"source":"Crossref","is-referenced-by-count":1,"title":["Functional Characterization of Endogenously Expressed Human RYR1 Variants"],"prefix":"10.3791","author":[{"given":"Susan","family":"Treves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Girard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zorzato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2098","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"issue":"7","key":"ref1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.nmd.2013.03.008","type":"journal-article","article-title":"Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis","volume":"23","author":"Dlamini","year":"2013","unstructured":"Dlamini, N. et al. Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. Neuromuscular Disorders. 23 (7), 540-548 (2013).","journal-title":"Neuromuscular Disorders"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1002\/humu.22056","type":"journal-article","article-title":"Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies","volume":"33","author":"Klein","year":"2012","unstructured":"Klein, A. et al. Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies. Human Mutation. 33, 981-988 (2012).","journal-title":"Human Mutation"},{"issue":"20","key":"ref3","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/humu.20356","type":"journal-article","article-title":"Mutations in RYR1 in malignant hyperthermia and central core disease","volume":"27","author":"Robinson","year":"2006","unstructured":"Robinson. R., Carpenter, D., Shaw, M. A., Halsall, J., Hopkins, P. Mutations in RYR1 in malignant hyperthermia and central core disease. Human Mutation. 27 (20), 977-989 (2006).","journal-title":"Human Mutation"},{"issue":"50","key":"ref4","doi-asserted-by":"crossref","first-page":"19501","DOI":"10.1074\/jbc.RA118.004453","type":"journal-article","article-title":"Ca2+ mediated activation of the skeletal muscle ryanodine receptor ion channel","volume":"293","author":"Xu","year":"2018","unstructured":"Xu, L. et al. Ca2+ mediated activation of the skeletal muscle ryanodine receptor ion channel. Journal of Biological Chemistry. 293 (50), 19501-19509 (2018).","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/bj3010661","type":"journal-article","article-title":"Alteration of intracellular Ca2+ transients in COS-7 cells transfected with the cDNA encoding skeletal-muscle ryanodine receptor carrying a mutation associated with malignant hyperthermia","volume":"301","author":"Treves","year":"1994","unstructured":"Treves, S. et al. Alteration of intracellular Ca2+ transients in COS-7 cells transfected with the cDNA encoding skeletal-muscle ryanodine receptor carrying a mutation associated with malignant hyperthermia. Biochemical Journal. 301 (3), 661-665 (1994).","journal-title":"Biochemical Journal"},{"issue":"6569","key":"ref6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/380072a0","type":"journal-article","article-title":"Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor","volume":"389","author":"Nakai","year":"1996","unstructured":"Nakai, J. et al. Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature. 389 (6569), 72-75 (1996).","journal-title":"Nature"},{"issue":"81","key":"ref7","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.cell.2008.02.042","type":"journal-article","article-title":"RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice","volume":"133","author":"Durham","year":"2008","unstructured":"Durham, W. J. et al. RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice. Cell. 133 (81) 53-65 (2008).","journal-title":"Cell"},{"issue":"51","key":"ref8","doi-asserted-by":"crossref","first-page":"21813","DOI":"10.1073\/pnas.0912126106","type":"journal-article","article-title":"Ca2+ dysregulation in Ryr1(I4895T\/wt) mice causes congenital myopathy with progressive formation of minicores, cores, and nemaline rods","volume":"106","author":"Zvaritch","year":"2009","unstructured":"Zvaritch, E. et al. Ca2+ dysregulation in Ryr1(I4895T\/wt) mice causes congenital myopathy with progressive formation of minicores, cores, and nemaline rods. Proceedings of the National Academy of Sciences of the United States of America. 106 (51) 21813-21818 (2009).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"10331","DOI":"10.1074\/jbc.RA120.013846","type":"journal-article","article-title":"Bi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice","volume":"295","author":"Elbaz","year":"2020","unstructured":"Elbaz., M. et al. Bi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice. Journal of Biological Chemistry. 295, 10331-10339 (2020).","journal-title":"Journal of Biological Chemistry"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1172\/JCI993","type":"journal-article","article-title":"Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia susceptible and normal individuals","volume":"101","author":"Censier","year":"1998","unstructured":"Censier, K., Urwyler, A., Zorzato, F., Treves, S. Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia susceptible and normal individuals. Journal of Clinical Investigations. 101 (6), 1233-1242. (1998).","journal-title":"Journal of Clinical Investigations"},{"issue":"51","key":"ref11","doi-asserted-by":"crossref","first-page":"48077","DOI":"10.1074\/jbc.M107134200","type":"journal-article","article-title":"B-lymphocytes from Malignant Hyperthermia-Susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators","volume":"276","author":"Girard","year":"2001","unstructured":"Girard, T. et al. B-lymphocytes from Malignant Hyperthermia-Susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators. Journal of Biological Chemistry. 276 (51), 48077-48982 (2001).","journal-title":"Journal of Biological Chemistry"},{"issue":"42","key":"ref12","doi-asserted-by":"crossref","first-page":"43838","DOI":"10.1074\/jbc.M403612200","type":"journal-article","article-title":"Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from Malignant Hyperthermia- Susceptible individuals and patients affected by Central Core Disease","volume":"279","author":"Ducreux","year":"2004","unstructured":"Ducreux, S. et al. Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from Malignant Hyperthermia- Susceptible individuals and patients affected by Central Core Disease. Journal of Biological Chemistry. 279 (42), 43838-43846 (2004).","journal-title":"Journal of Biological Chemistry"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1042\/BJ20051282","type":"journal-article","article-title":"Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes","volume":"395","author":"Ducreux","year":"2006","unstructured":"Ducreux, S. et al. Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes. Biochemical Journal. 395, 259-266 (2006).","journal-title":"Biochemical Journal"},{"issue":"25","key":"ref14","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1093\/hmg\/10.25.2879","type":"journal-article","article-title":"Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis","volume":"10","author":"Tilgen","year":"2001","unstructured":"Tilgen, N. et al. Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis. Human Molecular Genetics. 10 (25), 2879-2887 (2001).","journal-title":"Human Molecular Genetics"},{"issue":"3","key":"ref15","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/hmg\/ddq506","type":"journal-article","article-title":"Enhanced excitation-coupled Ca2+ entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease","volume":"20","author":"Treves","year":"2011","unstructured":"Treves, S. et al. Enhanced excitation-coupled Ca2+ entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease. Human Molecular Genetics. 20 (3), 589-600 (2011).","journal-title":"Human Molecular Genetics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.22209","type":"journal-article","article-title":"JP-45\/JSRP1 variants affect skeletal muscle excitation contraction coupling by decreasing the sensitivity of the dihydropyridine receptor","volume":"34","author":"Yasuda","year":"2013","unstructured":"Yasuda, T. et al. JP-45\/JSRP1 variants affect skeletal muscle excitation contraction coupling by decreasing the sensitivity of the dihydropyridine receptor. Human Mutation. 34, 184-190 (2013).","journal-title":"Human Mutation"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1074\/jbc.274.9.5995","type":"journal-article","article-title":"Skeletal muscle ryanodine receptor is involved in calcium signaling in human B lymphocytes","volume":"274","author":"Sei","year":"1999","unstructured":"Sei, Y., Gallagher, K. L., Basile, A: S. Skeletal muscle ryanodine receptor is involved in calcium signaling in human B lymphocytes. Journal of Biological Chemistry. 274 (9), 5995-6062 (1999).","journal-title":"Journal of Biological Chemistry"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1097\/00000542-199606000-00014","type":"journal-article","article-title":"Chlorocresol, an additive to commercial succinylcholine, induces contracture of human malignant Hyperthermia Susceptible muscles via activation of the ryanodine receptor Ca2+ channel","volume":"84","author":"Tegazzin","year":"1996","unstructured":"Tegazzin, V., Scutari, E., Treves, S., Zorzato, F. Chlorocresol, an additive to commercial succinylcholine, induces contracture of human malignant Hyperthermia Susceptible muscles via activation of the ryanodine receptor Ca2+ channel. Anesthesiology. 84, 1275-1279 (1996).","journal-title":"Anesthesiology"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1161\/CIRCULATIONAHA.117.032703","type":"journal-article","article-title":"Ryanodine receptor calcium leak in circulating B-lymphocytes as a biomarker for heart failure","volume":"138","author":"Kushnir","year":"2018","unstructured":"Kushnir, A. et al. Ryanodine receptor calcium leak in circulating B-lymphocytes as a biomarker for heart failure. Circulation. 138 (11), 1144-1154 (2018).","journal-title":"Circulation"},{"issue":"4","key":"ref20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/humu.20991","type":"journal-article","article-title":"Functional characterization of ryanodine receptor sequence variants using a metabolic assay in immortalized B-lymphocytes","volume":"30","author":"Zullo","year":"2009","unstructured":"Zullo, A. et al. Functional characterization of ryanodine receptor sequence variants using a metabolic assay in immortalized B-lymphocytes. Human Mutation. 30 (4), E575-E590 (2009).","journal-title":"Human Mutation"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"33372","DOI":"10.1038\/srep33372","type":"journal-article","article-title":"Hypermetabolism in B-lymphocytes from malignant hyperthermia susceptible individuals","volume":"6","author":"Hoppe","year":"2016","unstructured":"Hoppe, K. et al. Hypermetabolism in B-lymphocytes from malignant hyperthermia susceptible individuals. Scientific Reports. 6, 33372 (2016).","journal-title":"Scientific Reports"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1093\/hmg\/ddg121","type":"journal-article","article-title":"A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia","volume":"12","author":"Monnier","year":"2003","unstructured":"Monnier, N. et al. A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia. Human Molecular Genetics. 12, 1171-1178 (2003).","journal-title":"Human Molecular Genetics"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00401-016-1656-8","type":"journal-article","article-title":"Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy","volume":"133","author":"Schartner","year":"2017","unstructured":"Schartner, V. et al. Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy Acta Neuropathologica. 133, 517-533 (2017).","journal-title":"Acta Neuropathologica"},{"key":"ref24","first-page":"1","type":"journal-article","article-title":"Alterations of excitation-contraction coupling and excitation coupled Ca2+ entry in human myotubes carrying CAV3 mutations linked to rippling muscle disease","volume":"32","author":"Ullrich","year":"2010","unstructured":"Ullrich, N. D. et al. Alterations of excitation-contraction coupling and excitation coupled Ca2+ entry in human myotubes carrying CAV3 mutations linked to rippling muscle disease. Human Mutation. 32, 1-9 (2010).","journal-title":"Human Mutation"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1042\/BJ20130698","type":"journal-article","article-title":"Characterization of a human skeletal muscle- derived cell line: biochemical, cellular and electrophysiological characterization","volume":"455","author":"Rokach","year":"2013","unstructured":"Rokach, O. et al. Characterization of a human skeletal muscle- derived cell line: biochemical, cellular and electrophysiological characterization. Biochemical Journal. 455, 169-177 (2013).","journal-title":"Biochemical Journal"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1093\/hmg\/ddl221","type":"journal-article","article-title":"Characterization of RYR1 mutations in core myopathies","volume":"15","author":"Zhou","year":"2006","unstructured":"Zhou, H. et al. Characterization of RYR1 mutations in core myopathies. Human Molecular Genetics. 15, 2791-2803 (2006).","journal-title":"Human Molecular Genetics"},{"key":"ref27","first-page":"1043","type":"journal-article","article-title":"Detection of proton release from cultured human myotubes to identify malignant hyperthermia susceptibility","volume":"97","author":"Klinger","year":"2002","unstructured":"Klinger, W., Baur, C., Georgieff, M., Lehmann-Horn, F., Melzer, W. Detection of proton release from cultured human myotubes to identify malignant hyperthermia susceptibility. Anesthesiology. 97, 1043-1056 (2002).","journal-title":"Anesthesiology"}],"container-title":["Journal of Visualized Experiments"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jove.com\/t\/62196\/functional-characterization-endogenously-expressed-human-ryr1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:28:36Z","timestamp":1792618116000},"score":1,"resource":{"primary":{"URL":"https:\/\/app.jove.com\/t\/62196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,9]]},"references-count":27,"journal-issue":{"issue":"172","published-online":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.3791\/62196","relation":{},"ISSN":["1940-087X"],"issn-type":[{"value":"1940-087X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,9]]}}}