{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T22:14:36Z","timestamp":1766182476689,"version":"3.41.2"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010425","name":"Tri-Service General Hospital","doi-asserted-by":"publisher","award":["TSGH\u2010C01\u2010113032"],"award-info":[{"award-number":["TSGH\u2010C01\u2010113032"]}],"id":[{"id":"10.13039\/501100010425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Phosphodiesterase inhibitors regulate intracellular Ca<jats:sup>2+<\/jats:sup> of cardiomyocytes through enhancing second messenger signalling. This study aimed to investigate whether TP\u201010, a selective phosphodiesterase10A inhibitor, modulates Ca<jats:sup>2+<\/jats:sup> cycling, attenuating arrhythmogenesis in the right ventricular outflow tract (RVOT). Right ventricular tissues from New Zealand white rabbits were harvested, and electromechanical analyses of ventricular tissues were conducted. Intracellular Ca<jats:sup>2+<\/jats:sup> was monitored using Fluo\u20103, and ionic current was recorded using patch\u2010clamp in isolated cardiomyocytes. Tissues from RVOT exhibited a reduction in action potential duration at both 50% and 90% repolarisation following treatment with TP\u201010. This treatment also inhibited burst firing induced by isoproterenol (ISO) in RVOT tissues, an effect that was nullified by thapsigargin. The protein kinase G inhibitor KT5823, whether used alone or in conjunction with TP\u201010, also suppressed ISO\u2010induced burst firing in these tissues. Compared to the control group, RVOT cardiomyocytes treated with TP\u201010 demonstrated enhanced amplitudes of Ca<jats:sup>2+<\/jats:sup> transients and increased stores of Ca<jats:sup>2+<\/jats:sup> in the sarcoplasmic reticulum. Although the L\u2010type Ca<jats:sup>2+<\/jats:sup> current was diminished in TP\u201010\u2010treated cardiomyocytes, the current from the Na<jats:sup>+<\/jats:sup>\u2010Ca<jats:sup>2+<\/jats:sup> exchanger was elevated. Furthermore, the density of late Na<jats:sup>+<\/jats:sup> current was significantly reduced in these treated cardiomyocytes. TP\u201010 administration also resulted in increased levels of calcium regulatory proteins, specifically phosphorylated phospholamban at Thr17 and sarcoplasmic\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> ATPase 2a. Our findings indicate that TP\u201010 attenuates ISO\u2010induced arrhythmic events in RVOT tissues via cGMP\u2010mediated modulation of intracellular Ca<jats:sup>2+<\/jats:sup> regulation.<\/jats:p>","DOI":"10.1111\/jcmm.70480","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T09:02:10Z","timestamp":1741770130000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phosphodiesterase <scp>10A<\/scp> Inhibitor Modulates Right Ventricular Outflow Tract Electrophysiological Activities and Calcium Homeostasis via the <scp>cGMP<\/scp>\/<scp>PKG<\/scp> Pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Feng\u2010Zhi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Institute of Physiology National Defense Medical Center  Taipei 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