{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:28:43Z","timestamp":1791210523454,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,2,17]]},"abstract":"\n \n Rationale:<\/jats:underline>\n <\/jats:title>\n \n Diastolic spontaneous Ca\n 2+<\/jats:sup>\n waves (DCWs) are recognized as important contributors to triggered arrhythmias. DCWs are thought to arise when [Ca\n 2+<\/jats:sup>\n ] in sarcoplasmic reticulum ([Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n ) reaches a certain threshold level, which might be reduced in cardiac disease as a consequence of sensitization of ryanodine receptors (RyR2s) to luminal Ca\n 2+<\/jats:sup>\n .\n <\/jats:p>\n <\/jats:sec>\n \n \n Objective:<\/jats:underline>\n <\/jats:title>\n We investigated the mechanisms of DCW generation in myocytes from normal and diseased hearts, using a canine model of post\u2013myocardial infarction ventricular fibrillation (VF).<\/jats:p>\n <\/jats:sec>\n \n \n Methods and Results:<\/jats:underline>\n <\/jats:title>\n \n The frequency of DCWs, recorded during periodic pacing in the presence of a \u03b2-adrenergic receptor agonist isoproterenol, was significantly higher in VF myocytes than in normal controls. Rather than occurring immediately on reaching a final [Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n , DCWs arose with a distinct time delay after attaining steady [Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n in both experimental groups. Although the rate of [Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n recovery after the SR Ca\n 2+<\/jats:sup>\n release was similar between the groups, in VF myocytes the latency to DCWs was shorter, and the [Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n at DCW initiation was lower. The restitution of depolarization-induced Ca\n 2+<\/jats:sup>\n transients, assessed by a 2-pulse protocol, was significantly faster in VF myocytes than in controls. The VF-related alterations in myocyte Ca\n 2+<\/jats:sup>\n cycling were mimicked by the RyR2 agonist, caffeine. The reducing agent, mercaptopropionylglycine, or the CaMKII inhibitor, KN93, decreased DCW frequency and normalized restitution of Ca\n 2+<\/jats:sup>\n release in VF myocytes.\n <\/jats:p>\n <\/jats:sec>\n \n \n Conclusions:<\/jats:underline>\n <\/jats:title>\n \n The attainment of a certain threshold [Ca\n 2+<\/jats:sup>\n ]\n SR<\/jats:sub>\n is not sufficient for the generation of DCWs. Postrelease Ca\n 2+<\/jats:sup>\n signaling refractoriness critically influences the occurrence of DCWs. Shortened Ca\n 2+<\/jats:sup>\n signaling refractoriness due to RyR2 phosphorylation and oxidation is responsible for the increased rate of DCWs observed in VF myocytes and could provide a substrate for synchronization of arrhythmogenic events at the tissue level in hearts prone to VF.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circresaha.111.260455","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T06:19:54Z","timestamp":1325830794000},"page":"569-577","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Shortened Ca\n 2+<\/sup>\n Signaling Refractoriness Underlies Cellular Arrhythmogenesis in a Postinfarction Model of Sudden Cardiac Death"],"prefix":"10.1161","volume":"110","author":[{"given":"Andriy E.","family":"Belevych","sequence":"first","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Terentyev","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radmila","family":"Terentyeva","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Ting","family":"Ho","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Gyorke","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M.","family":"Bonilla","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia A.","family":"Carnes","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Billman","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandor","family":"Gy\u00f6rke","sequence":"additional","affiliation":[{"name":"From the Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, College of Medicine (A.E.B., D.T., R.T., H.-T.H., I.G., I.B. C.A.C., G.E.B., S.G.), and College of Pharmacy (I.B., C.A.C.), The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192667"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.683235"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2006"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.10.012"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223586"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm038"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000032490.04207.BD"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000146029.80463.7d"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086496"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm009"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706573104"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(88)90005-X"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.227744"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.01.002"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.69.4.790"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90583.2008"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000233386.02708.72"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp246"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050475"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000252828.17939.00"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.183475"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.153007"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060116"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2003.12.002"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.11.081"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.176677"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.229294"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00030.2007"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018305"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2011.01.017"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.175547"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2008.12.3944"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.04.032"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.02.019"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.2741\/3591"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5348.234"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.2741\/ikemoto"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.01.064"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.09.020"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr025"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.108.811539"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.111.260455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:56:52Z","timestamp":1766159812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.111.260455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,17]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,2,17]]}},"alternative-id":["10.1161\/CIRCRESAHA.111.260455"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.111.260455","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,17]]},"assertion":[{"value":"2011-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-12-06","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-12-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}