{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:28:38Z","timestamp":1793158118976,"version":"4.5.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p> Early afterdepolarizations (EADs) have been implicated in severe cardiac arrhythmias and sudden cardiac deaths. However, the mechanism(s) for EAD genesis, especially regarding the relative contribution of Ca<jats:sup>2+<\/jats:sup> wave (CaW) vs. L-type Ca current ( I<jats:sub>Ca,L<\/jats:sub>), still remains controversial. In the present study, we simultaneously recorded action potentials (APs) and intracellular Ca<jats:sup>2+<\/jats:sup> images in isolated rabbit ventricular myocytes and systematically compared the properties of EADs in the following two pharmacological models: 1) hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>; 200 \u03bcM); and 2) isoproterenol (100 nM) and BayK 8644 (50 nM) (Iso + BayK). We assessed the rate dependency of EADs, the temporal relationship between EADs and corresponding CaWs, the distribution of EADs over voltage, and the effects of blockers of I<jats:sub>Ca,L<\/jats:sub>, Na\/Ca exchangers, and ryanodine receptors. The most convincing evidence came from the AP-clamp experiment, in which the cell membrane clamp was switched from current clamp to voltage clamp using a normal AP waveform without EAD; CaWs disappeared in the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> model, but persisted in the Iso + BayK model. We postulate that, although CaWs and reactivation of I<jats:sub>Ca,L<\/jats:sub> may act synergistically in either case, reactivation of I<jats:sub>Ca,L<\/jats:sub> plays a predominant role in EAD genesis under oxidative stress (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> model), while spontaneous CaWs are a predominant cause for EADs under Ca<jats:sup>2+<\/jats:sup> overload condition (Iso + BayK model). <\/jats:p>","DOI":"10.1152\/ajpheart.00742.2011","type":"journal-article","created":{"date-parts":[[2012,2,4]],"date-time":"2012-02-04T07:00:22Z","timestamp":1328338822000},"page":"H1636-H1644","source":"Crossref","is-referenced-by-count":94,"title":["Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents?"],"prefix":"10.1152","volume":"302","author":[{"given":"Zhenghang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry 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