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Previous studies reported depressed left ventricular function in DMD patients which may result from deranged intracellular Ca<jats:sup>2+<\/jats:sup>\u2010handling. To decipher the mechanism(s) underlying the depressed LV function, we tested the hypothesis that iPSC\u2010CMs generated from DMD patients feature blunted positive inotropic response to \u03b2\u2010adrenergic stimulation. To test the hypothesis, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transients and contractions were recorded from healthy and DMD\u2010CMs. While in healthy CMs (HC) isoproterenol caused a prominent positive inotropic effect, DMD\u2010CMs displayed a blunted inotropic response. Next, we tested the functionality of the sarcoplasmic reticulum (SR) by measuring caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> release. In contrast to HC, DMD\u2010CMs exhibited reduced caffeine\u2010induced Ca<jats:sup>2+<\/jats:sup> signal amplitude and recovery time. In support of the depleted SR Ca<jats:sup>2+<\/jats:sup> stores hypothesis, in DMD\u2010CMs the negative inotropic effects of ryanodine and cyclopiazonic acid were smaller than in HC. RNA\u2010seq analyses demonstrated that in DMD CMs the RNA\u2010expression levels of specific subunits of the L\u2010type calcium channel, the \u03b21\u2010adrenergic receptor (ADR\u03b21) and adenylate cyclase were down\u2010regulated by 3.5\u2010, 2.8\u2010 and 3\u2010fold, respectively, which collectively contribute to the depressed \u03b2\u2010adrenergic responsiveness.<\/jats:p>","DOI":"10.1111\/jcmm.16341","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T04:20:04Z","timestamp":1614054004000},"page":"3922-3934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Depressed \u03b2\u2010adrenergic inotropic responsiveness and intracellular calcium handling abnormalities in Duchenne Muscular Dystrophy patients\u2019 induced pluripotent stem cell\u2013derived cardiomyocytes"],"prefix":"10.1111","volume":"25","author":[{"given":"Lucy 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