{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:12:12Z","timestamp":1791209532833,"version":"4.1.0"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,10,1]]},"abstract":"<jats:p>Abnormalities in cardiomyocyte Ca2+ handling contribute to impaired contractile function in heart failure (HF). Experiments on single ryanodine receptors (RyRs) incorporated into lipid bilayers have indicated that RyRs from failing hearts are more active than those from healthy hearts. Here, we analyzed spontaneous Ca2+ sparks (brief, localized increased in [Ca2+]i) to evaluate RyR cluster activity in situ in a mouse post-myocardial infarction (PMI) model of HF. The cardiac ejection fraction of PMI mice was reduced to \u223c30% of that of sham-operated (sham) mice, and their cardiomyocytes were hypertrophied. The [Ca2+]i transient amplitude and sarcoplasmic reticulum (SR) Ca2+ load were decreased in intact PMI cardiomyocytes compared with those from sham mice, and spontaneous Ca2+ sparks were less frequent, whereas the fractional release and the frequency of Ca2+ waves were both increased, suggesting higher RyR activity. In permeabilized cardiomyocytes, in which the internal solution can be controlled, Ca2+ sparks were more frequent in PMI cells (under conditions of similar SR Ca2+ load), confirming the enhanced RyR activity. However, in intact cells from PMI mice, the Ca2+ sparks frequency normalized by the SR Ca2+ load in that cell were reduced compared with those in sham mice, indicating that the cytosolic environment in intact cells contributes to the decrease in Ca2+ spark frequency. Indeed, using an internal \u201cfailing solution\u201d with less ATP (as found in HF), we observed a dramatic decrease in Ca2+ spark frequency in permeabilized PMI and sham myocytes. In conclusion, our data show that, even if isolated RyR channels show more activity in HF, concomitant alterations in intracellular media composition and SR Ca2+ load may mask these effects at the Ca2+ spark level in intact cells. Nonetheless, in this scenario, the probability of arrhythmogenic Ca2+ waves is enhanced, and they play a potential role in the increase in arrhythmia events in HF patients.<\/jats:p>","DOI":"10.1085\/jgp.201511366","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T01:39:40Z","timestamp":1442281180000},"page":"295-306","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Reconciling depressed Ca2+ sparks occurrence with enhanced RyR2 activity in failing mice cardiomyocytes"],"prefix":"10.1085","volume":"146","author":[{"given":"Gema","family":"Ruiz-Hurtado","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR-S 1180, LabEx LERMIT, DHU TORINO 1 , and 2"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France 1 , and 2"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR-S 1180, LabEx LERMIT, DHU TORINO 1 , and 2"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France 1 , and 2"},{"name":"Instituto de Investigaci\u00f3n, Hospital 12 de Octubre, 28041 Madrid, Spain 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linwei","family":"Li","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR-S 1180, LabEx LERMIT, DHU TORINO 1 , and 2"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, 92296 Ch\u00e2tenay-Malabry, France 1 , and 2"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), UMR-S 1180, LabEx LERMIT, DHU TORINO 1 , and 2"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, 92296 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