{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T12:12:42Z","timestamp":1754395962236,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pacing Clinical Electrophis"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli\u2013extra\u2010stimulus (S<jats:sub>1<\/jats:sub>\u2013S<jats:sub>2<\/jats:sub>) method and dynamic S<jats:sub>1<\/jats:sub> pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol\u201012\u2010myristate\u201013\u2010acetate (PMA) (100\u00a0nM) (<jats:italic>n<\/jats:italic>\u00a0=\u00a015) greatly steepened the restitution curves (<jats:italic>S<\/jats:italic><jats:sub>max\u00a0<\/jats:sub>&gt;\u00a01) (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01) at each site compared to the control group (<jats:italic>n<\/jats:italic>\u00a0=\u00a015). Furthermore, treatment with PMA also induced larger spatial dispersions of <jats:italic>S<\/jats:italic><jats:sub>max<\/jats:sub> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05) and decreased the thresholds of the VA and APD alternans (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500\u00a0nM) (<jats:italic>n<\/jats:italic>\u00a0=\u00a010), reversibly flattened the APD restitution curves at each site (<jats:italic>S<\/jats:italic><jats:sub>max\u00a0<\/jats:sub>&lt;\u00a01), decreased the spatial dispersions of <jats:italic>S<\/jats:italic><jats:sub>max<\/jats:sub>, and increased the thresholds of APD alternans and VA. According to the results of patch\u2010clamp, peak amplitude of L\u2010type Ca<jats:sup>2+<\/jats:sup> current was significantly increased by addition of PMA compared with control (CTL) group (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.05). Antagonize this current with verapamil (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) can fully inhibited the PMA induced increasing of <jats:italic>S<\/jats:italic><jats:sub>max<\/jats:sub> and inducibility of VA and alternans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca<jats:sup>2+<\/jats:sup> influx.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pace.14998","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T11:59:40Z","timestamp":1719316780000},"page":"1131-1140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L\u2010type Ca<sup>+<\/sup> current"],"prefix":"10.1111","volume":"47","author":[{"given":"Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology Jinshan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-2701","authenticated-orcid":false,"given":"Jianing","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuhua","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Cardiology Jinshan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute of Wuhan University  Wuhan 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