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Ca-Alts appear to result from a variation in the amount of Ca2+ released from the sarcoplasmic reticulum (SR) between two consecutive heartbeats. This variable Ca2+ release has been attributed to the alternation of the action potential duration, delay in the recovery from inactivation of RYR Ca2+ release channel (RYR2), or an incomplete Ca2+ refilling of the SR. In all three cases, the RYR2 mobilizes less Ca2+ from the SR in an alternating manner, thereby generating an alternating profile of the Ca2+ transients. We used a new experimental approach, fluorescence local field optical mapping (FLOM), to record at the epicardial layer of an intact heart with subcellular resolution. In conjunction with a local cold finger, a series of images were recorded within an area where the local cooling induced a temperature gradient. Ca-Alts were larger in colder regions and occurred without changes in action potential duration. Analysis of the change in the enthalpy and Q10 of several kinetic processes defining intracellular Ca2+ dynamics indicated that the effects of temperature change on the relaxation of intracellular Ca2+ transients involved both passive and active mechanisms. The steep temperature dependency of Ca-Alts during tachycardia suggests Ca-Alts are generated by insufficient SERCA-mediated Ca2+ uptake into the SR. We found that Ca-Alts are heavily dependent on intra-SR Ca2+ and can be promoted through partial pharmacologic inhibition of SERCA2a. Finally, the FLOM experimental approach has the potential to help us understand how arrhythmogenesis correlates with the spatial distribution of metabolically impaired myocytes along the myocardium.<\/jats:p>","DOI":"10.1085\/jgp.202012568","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T19:14:01Z","timestamp":1610565241000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Thermal modulation of epicardial Ca2+ dynamics uncovers molecular mechanisms of Ca2+ alternans"],"prefix":"10.1085","volume":"153","author":[{"given":"Jose","family":"Millet","sequence":"first","affiliation":[{"name":"Institute of Information and Communication Technologies, Universitat Polit\u00e8cnica de Val\u00e8ncia and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares, Valencia, Spain 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-8877","authenticated-orcid":true,"given":"Yuriana","family":"Aguilar-Sanchez","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, Rush University Medical Center, Chicago, IL 2"},{"name":"School of Natural Sciences, University of California, Merced, Merced, CA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmytro","family":"Kornyeyev","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Engineering, University of California Merced, Merced, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-0688","authenticated-orcid":true,"given":"Maedeh","family":"Bazmi","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, University of California, Merced, Merced, CA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Fainstein","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad Nacional de Entre R\u00edos, Entre R\u00edos, Argentina 4"},{"name":"Department of Bioengineering, School of Engineering, University of California Merced, Merced, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio A.","family":"Copello","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-9546","authenticated-orcid":true,"given":"Ariel L.","family":"Escobar","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Engineering, University of California Merced, Merced, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"key":"2023072706131376500_bib1","first-page":"280","article-title":"Surface Electrocardiogram Predictors of Sudden Cardiac Arrest","volume":"16","author":"Abdelghani","year":"2016","journal-title":"Ochsner J."},{"key":"2023072706131376500_bib2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0022-0736(84)80057-6","article-title":"Fluctuations in T-wave morphology and susceptibility to ventricular fibrillation","volume":"17","author":"Adam","year":"1984","journal-title":"J. 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