{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:52:58Z","timestamp":1773888778191,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100005153","name":"China National Funds for Distinguished Young Scientists","doi-asserted-by":"publisher","award":["11125419"],"award-info":[{"award-number":["11125419"]}],"id":[{"id":"10.13039\/501100005153","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005153","name":"China National Funds for Distinguished Young Scientists","doi-asserted-by":"publisher","award":["10925525"],"award-info":[{"award-number":["10925525"]}],"id":[{"id":"10.13039\/501100005153","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005153","name":"China National Funds for Distinguished Young Scientists","doi-asserted-by":"publisher","award":["11125419"],"award-info":[{"award-number":["11125419"]}],"id":[{"id":"10.13039\/501100005153","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005153","name":"China National Funds for Distinguished Young Scientists","doi-asserted-by":"publisher","award":["10925525"],"award-info":[{"award-number":["10925525"]}],"id":[{"id":"10.13039\/501100005153","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Scientific World Journal"],"published-print":{"date-parts":[[2014]]},"abstract":"<jats:p>The mechanism of isoprenaline exerting its effects on cardiac pacemaking and driving in sick sinus syndrome is controversial and unresolved. In this paper, mathematical models for rabbit sinoatrial node cells were modified by incorporating equations for the known dose-dependent actions of isoprenaline on various ionic channel currents, the intracellular Ca<jats:sup>2+<\/jats:sup>transient, and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:msub><mml:mi>i<\/mml:mi><mml:mrow><mml:mtext>Na<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>changes induced by SCN5A gene mutations; the cell models were also incorporated into an intact SAN-atrium model of the rabbit heart that is based on both heterogeneities of the SAN electrophysiology and histological structure. Our results show that, in both central and peripheral cell models, isoprenaline could not only shorten the action potential duration, but also increase the amplitude of action potential. The mutation impaired the SAN pacemaking. Simulated vagal nerve activity amplified the bradycardic effects of the mutation. However, in tissue case, the pacemaker activity may show temporal, spatial, or even spatiotemporal cessation caused by the mutation. Addition of isoprenaline could significantly diminish the bradycardic effect of the mutation and the SAN could restart pacing and driving the surrounding tissue. Positive effects of isoprenaline may primarily be attributable to an increase in<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:msub><mml:mi>i<\/mml:mi><mml:mrow><mml:mtext>Na<\/mml:mtext><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>and<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mrow><mml:msub><mml:mi>i<\/mml:mi><mml:mrow><mml:mtext>Ca,<\/mml:mtext><mml:mi>T<\/mml:mi><\/mml:mrow><\/mml:msub><\/mml:mrow><\/mml:math>which were reduced by the mutation.<\/jats:p>","DOI":"10.1155\/2014\/540496","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T01:51:14Z","timestamp":1390355474000},"page":"1-11","source":"Crossref","is-referenced-by-count":5,"title":["Isoprenaline: A Potential Contributor in Sick Sinus Syndrome\u2014Insights from a Mathematical Model of the Rabbit Sinoatrial Node"],"prefix":"10.1155","volume":"2014","author":[{"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Physics and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Physics and Electronic Information, Anhui Normal University, Wuhu 241000, China"},{"name":"Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Manchester M139PL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-wei","family":"Shuai","sequence":"additional","affiliation":[{"name":"Department of Physics and Institute of Theoretical Physics and Astrophysics, Xiamen University, Xiamen 361005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"8","key":"1","first-page":"1725","volume":"67","year":"2003","journal-title":"American Family Physician"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eup014"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.01.170"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010985"},{"key":"5","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1007\/s11427-013-4533-x","volume":"56","year":"2013","journal-title":"Science China Life Sciences"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2009.01963.x"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2569"},{"issue":"1","key":"8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0002-8703(75)90253-7","volume":"90","year":"1975","journal-title":"American Heart Journal"},{"issue":"1","key":"9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00582621","volume":"388","year":"1980","journal-title":"Pflugers Archiv European Journal of Physiology"},{"issue":"2","key":"10","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/BF00582323","volume":"411","year":"1988","journal-title":"Pflugers Archiv European Journal of Physiology"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000266742.51389.a4"},{"issue":"5719","key":"12","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/280235a0","volume":"280","year":"1979","journal-title":"Nature"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00150-0"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010122108"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201010488"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.107.112854"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.219949"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000152100.04087.DB"},{"issue":"1","key":"18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/01.RES.46.1.11","volume":"46","year":"1980","journal-title":"Circulation Research"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01101.2005"},{"issue":"1","key":"19","first-page":"H397","volume":"279","year":"2000","journal-title":"American Journal of Physiology"},{"key":"22","first-page":"241","volume":"3","year":"2012","journal-title":"Frontiers in Physiology"},{"issue":"2","key":"24","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1113\/jphysiol.1996.sp021220","volume":"491","year":"1996","journal-title":"Journal of Physiology"},{"issue":"1","key":"25","first-page":"27","volume":"85","year":"2000","journal-title":"Experimental Physiology"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00459-X"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01118.2008"},{"issue":"5","key":"38","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1136\/hrt.33.5.639","volume":"33","year":"1971","journal-title":"British Heart Journal"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.068734"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00143.2010"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0793u.x"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1161\/hh0102.102271"},{"issue":"5","key":"32","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1046\/j.1540-8167.2002.00465.x","volume":"13","year":"2002","journal-title":"Journal of Cardiovascular Electrophysiology"},{"issue":"6","key":"33","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/clc.4960030606","volume":"3","year":"1980","journal-title":"Clinical Cardiology"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.02.024"},{"issue":"2","key":"35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1161\/01.CIR.81.2.537","volume":"81","year":"1990","journal-title":"Circulation"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1007\/BF00235442"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(02)00135-3"}],"container-title":["The Scientific World Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/tswj\/2014\/540496.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/tswj\/2014\/540496.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/tswj\/2014\/540496.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T02:26:01Z","timestamp":1498098361000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/tswj\/2014\/540496\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014]]},"references-count":37,"alternative-id":["540496","540496"],"URL":"https:\/\/doi.org\/10.1155\/2014\/540496","relation":{},"ISSN":["2356-6140","1537-744X"],"issn-type":[{"value":"2356-6140","type":"print"},{"value":"1537-744X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014]]}}}