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PA may lead to several types of cardiomyopathy and has been linked to cardiac electrical abnormalities such as QT interval prolongation, life\u2010threatening arrhythmias, and sudden cardiac death. To gain insights into the mechanisms underlying PA\u2010induced proarrhythmia, we recorded action potentials (APs) and ion currents using whole\u2010cell patch\u2010clamp in ventricular\u2010like induced pluripotent stem cells\u2010derived cardiomyocytes (hiPSC\u2010CMs) from a PA patient carrying two pathogenic mutations in the\n                    <jats:italic>PCCA<\/jats:italic>\n                    gene (p.Cys616_Val633del and p.Gly477Glufs*9) (PCCA cells) and from a healthy subject (healthy cells). In cells driven at 1\u2009Hz, PCC deficiency increased the latency and prolonged the AP duration (APD) measured at 20% of repolarization, without modifying resting membrane potential or AP amplitude. Moreover, delayed afterdepolarizations appeared at the end of the repolarization phase in unstimulated and paced PCCA cells. PCC deficiency significantly reduced peak sodium current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    ) but increased the late\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>NaL<\/jats:sub>\n                    ) component. In addition, L\u2010type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>CaL<\/jats:sub>\n                    ) density was reduced, while the inward and outward density of the Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>NCX<\/jats:sub>\n                    ) was increased in PCCA cells compared to healthy ones. In conclusion, our results demonstrate that at the cellular level, PCC deficiency can modify the ion currents controlling cardiac excitability, APD, and intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling, increasing the risk of arrhythmias independently of the progressive late\u2010onset cardiomyopathy induced by PA disease.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70030","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T02:41:05Z","timestamp":1745980865000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Propionic Acidemia\u2010Induced Proarrhythmic Electrophysiological Alterations in Human\n                    <scp>iPSC<\/scp>\n                    \u2010Derived Cardiomyocytes"],"prefix":"10.1002","volume":"48","author":[{"given":"Anabel","family":"C\u00e1mara\u2010Checa","sequence":"first","affiliation":[{"name":"Department 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