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However, no model has been reported that can induce C\u2010ALT in\u00a0vitro using human cells, and the developmental mechanism of C\u2010ALT has not been studied using human cells. In this study, we successfully induced C\u2010ALT in\u00a0vitro using human\u2010induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs). By stimulating \u03b2\u2010adrenergic receptor with isoproterenol on hiPSC\u2010CMs cultured in atmospheric condition (with ~0.04% CO<jats:sub>2<\/jats:sub>), contractility and calcium transient were observed to alternately increase and decrease with each beat. In contrast, C\u2010ALT was not induced in hiPSC\u2010CMs cultured at 5% CO<jats:sub>2<\/jats:sub> concentration. Since previous studies have linked C\u2010ALT to problems with calcium regulation in the sarcoplasmic reticulum (SR), we exposed hiPSC\u2010CMs to compounds that alter SR Ca<jats:sup>2+<\/jats:sup> loading and analyzed their contractile responses. The results showed that exposure to verapamil, thapsigargin, and ryanodine either suppressed or eliminated C\u2010ALT. In contrast, omecamtiv mecarbil and blebbistatin, which alter contractility without SR Ca<jats:sup>2+<\/jats:sup> loading, did not induce or suppress C\u2010ALT. These results suggest that C\u2010ALT in hiPSC\u2010CMs induced by isoproterenol may be due to abnormal regulation of the ryanodine receptor's opening and closing caused by excessive Ca<jats:sup>2+<\/jats:sup> load in the SR from \u03b2\u2010adrenergic receptor stimulation.<\/jats:p>","DOI":"10.14814\/phy2.70152","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T03:42:02Z","timestamp":1735011722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Induction of cardiac alternans in human <scp>iPS<\/scp>\u2010derived cardiomyocytes through \u03b2\u2010adrenergic receptor stimulation"],"prefix":"10.14814","volume":"12","author":[{"given":"Yuto","family":"Hinata","sequence":"first","affiliation":[{"name":"Ogino Memorial Laboratory Nihon Kohden Corporation, TWIns  Shinjuku\u2010ku Tokyo Japan"},{"name":"Institute of Advanced Biomedical Engineering and Science TWIns, Tokyo Women's 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