{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:12:19Z","timestamp":1769040739179,"version":"3.49.0"},"reference-count":79,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Impaired calcium (Ca<jats:sup>2+<\/jats:sup>) signalling is the main contributor to depressed ventricular contractile function and occurrence of arrhythmia in heart failure (HF).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here we report that in atrial cells of a rabbit HF model, Ca<jats:sup>2+<\/jats:sup> signalling is enhanced and we identified the underlying cellular mechanisms. Enhanced Ca<jats:sup>2+<\/jats:sup> transients (CaTs) are due to upregulation of inositol\u20101,4,5\u2010trisphosphate receptor induced Ca<jats:sup>2+<\/jats:sup> release (IICR) and decreased mitochondrial Ca<jats:sup>2+<\/jats:sup> sequestration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Enhanced IICR, however, together with an increased activity of the sodium\u2013calcium exchange mechanism, also facilitates spontaneous Ca<jats:sup>2+<\/jats:sup> release in form of arrhythmogenic Ca<jats:sup>2+<\/jats:sup> waves and spontaneous action potentials, thus enhancing the arrhythmogenic potential of atrial cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data show that enhanced Ca<jats:sup>2+<\/jats:sup> signalling in HF provides atrial cells with a mechanism to improve ventricular filling and to maintain cardiac output, but also increases the susceptibility to develop atrial arrhythmias facilitated by spontaneous Ca<jats:sup>2+<\/jats:sup> release.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>We studied excitation\u2013contraction coupling (ECC) and inositol\u20101,4,5\u2010triphosphate (IP<jats:sub>3<\/jats:sub>)\u2010dependent Ca<jats:sup>2+<\/jats:sup> release in normal and heart failure (HF) rabbit atrial cells. Left ventricular HF was induced by combined volume and pressure overload. In HF atrial myocytes diastolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was increased, action potential (AP)\u2010induced Ca<jats:sup>2+<\/jats:sup> transients (CaTs) were larger in amplitude, primarily due to enhanced Ca<jats:sup>2+<\/jats:sup> release from central non\u2010junctional sarcoplasmic reticulum (SR) and centripetal propagation of activation was accelerated, whereas HF ventricular CaTs were depressed. The larger CaTs were due to enhanced IP<jats:sub>3<\/jats:sub> receptor\u2010induced Ca<jats:sup>2+<\/jats:sup> release (IICR) and reduced mitochondrial Ca<jats:sup>2+<\/jats:sup> buffering, consistent with a reduced mitochondrial density and Ca<jats:sup>2+<\/jats:sup> uptake capacity in HF. Elementary IP<jats:sub>3<\/jats:sub> receptor\u2010mediated Ca<jats:sup>2+<\/jats:sup> release events (Ca<jats:sup>2+<\/jats:sup> puffs) were more frequent in HF atrial myoctes and were detected more often in central regions of the non\u2010junctional SR compared to normal cells. HF cells had an overall higher frequency of spontaneous Ca<jats:sup>2+<\/jats:sup> waves and a larger fraction of waves (termed arrhythmogenic Ca<jats:sup>2+<\/jats:sup> waves) triggered APs and global CaTs. The higher propensity of arrhythmogenic Ca<jats:sup>2+<\/jats:sup> waves resulted from the combined action of enhanced IICR and increased activity of sarcolemmal Na<jats:sup>+<\/jats:sup>\u2013Ca<jats:sup>2+<\/jats:sup> exchange depolarizing the cell membrane. In conclusion, the data support the hypothesis that in atrial myocytes from hearts with left ventricular failure, enhanced CaTs during ECC exert positive inotropic effects on atrial contractility which facilitates ventricular filling and contributes to maintaining cardiac output. However, HF atrial cells were also more susceptible to developing arrhythmogenic Ca<jats:sup>2+<\/jats:sup> waves which might form the substrate for atrial rhythm disorders frequently encountered in HF.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.283226","type":"journal-article","created":{"date-parts":[[2014,11,22]],"date-time":"2014-11-22T05:10:06Z","timestamp":1416633006000},"page":"1459-1477","source":"Crossref","is-referenced-by-count":68,"title":["Inositol\u20101,4,5\u2010trisphosphate induced Ca<sup>2+<\/sup> release and excitation\u2013contraction coupling in atrial myocytes from normal and failing hearts"],"prefix":"10.1113","volume":"593","author":[{"given":"Felix","family":"Hohendanner","sequence":"first","affiliation":[{"name":"Department of Molecular Biophysics and Physiology Rush University Medical Center  Chicago IL 60612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Walther","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology Rush University Medical Center  Chicago IL 60612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua T.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology Rush University Medical Center  Chicago IL 60612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Kettlewell","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawsan","family":"Awad","sequence":"additional","affiliation":[{"name":"Rush Center for Congenital Heart Disease Rush University Medical Center  Chicago IL 60612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Godfrey L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow G12 8QQ UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassyl A.","family":"Lonchyna","sequence":"additional","affiliation":[{"name":"Section of Cardiac and Thoracic Surgery The University of Chicago Medicine  Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lothar A.","family":"Blatter","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Physiology Rush University Medical Center  Chicago IL 60612 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000194329.41863.89"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.39.020188.000353"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(92)93381-S"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020130"},{"issue":"1","key":"e_1_2_6_6_1","first-page":"I36","article-title":"Upregulated Na\/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure","volume":"97","author":"Bers DM","year":"2002","journal-title":"Basic Res Cardiol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(83)90317-X"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2007.05.004"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03223"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.01.030"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2446391"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.04.014"},{"key":"e_1_2_6_13_1","first-page":"664","article-title":"Changes of sarcoplamic reticular Ca2+\u2010ATPase and IP3\u2010I receptor mRNA expression in patients with atrial fibrillation","volume":"115","author":"Cao K","year":"2002","journal-title":"Chin Med J (Engl)"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.077180"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.5.880"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250502"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000212851"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.68.021915"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(97)89297-1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.08.030"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.12.021"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.012940"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.177576"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.236117"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01155.2007"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2013-304657"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.167387"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2006"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117739"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905485106"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300895"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021521"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)90734-G"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083715"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt087"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.02.016"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75903-6"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.05.014"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.03.007"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000172556.05576.4c"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.67.5.1045"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00624-2"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01559"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10669"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10223"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.239434"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00936.2011"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0813"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.261.6.C1123"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/415219a"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(86)90761-7"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.12.011"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00026-5"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00586.2006"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.4.1034"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.11.1009"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091193"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(75)90229-6"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(98)70217-0"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509645200"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00619.2005"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000093399.11734.B3"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.026963"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.103267"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.223446"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.34.4.531"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.113.3.469"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115855109"},{"key":"e_1_2_6_69_1","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1242\/jcs.114.22.3979","article-title":"Calcium puffs are generic InsP3\u2010activated elementary calcium signals and are downregulated by prolonged hormonal stimulation to inhibit cellular calcium responses","volume":"114","author":"Tovey SC","year":"2001","journal-title":"J\u00a0Cell Sci"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt018"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02373-2"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.07.006"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000072767.89944.6E"},{"key":"e_1_2_6_74_1","doi-asserted-by":"crossref","first-page":"H574","DOI":"10.1152\/ajpheart.1989.256.2.H574","article-title":"X\u2010ray microanalysis of single cardiac myocytes frozen under voltage\u2010clamp conditions","volume":"256","author":"Wendt\u2010Gallitelli MF","year":"1989","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.10.3710"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01144-5"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1159\/000095517"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.058529"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.197913"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00932.2012"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2014.283226","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2014.283226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:10:45Z","timestamp":1697292645000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2014.283226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,22]]},"references-count":79,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"alternative-id":["10.1113\/jphysiol.2014.283226"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2014.283226","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,22]]}}}