{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T05:08:11Z","timestamp":1725080891567},"reference-count":71,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:p>Endothelin-1 (ET-1) and activation of protein kinase C (PKC) have been implicated in alterations of myocyte function in cardiac hypertrophy and heart failure. Changes in cellular Ca<jats:sup>2+<\/jats:sup>handling and electrophysiological properties also occur in these states and may contribute to mechanical dysfunction and arrhythmias. While ET-1 or PKC stimulation induces cellular hypertrophy in cultured neonatal rat ventricular myocytes (NRVMs), a system widely used in studies of hypertrophic signaling, there is little data about electrophysiological changes. Here we studied the effects of ET-1 (100 nM) or the PKC activator phorbol 12-myristate 13-acetate (PMA, 1 \u03bcM) on ionic currents in NRVMs. The acute effects of PMA or ET-1 (\u226430 min) were small or insignificant. However, PMA or ET-1 exposure for 48\u201372 h increased cell capacitance by 100 or 25%, respectively, indicating cellular hypertrophy. ET-1 also slightly increased Ca<jats:sup>2+<\/jats:sup>current density (T and L type). Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup>exchange current was increased by chronic pretreatment with either PMA or ET-1. In contrast, transient outward and delayed rectifier K<jats:sup>+<\/jats:sup>currents were strongly downregulated by PMA or ET-1 pretreatment. Inward rectifier K<jats:sup>+<\/jats:sup>current tended toward a decrease at larger negative potential, but time-independent outward K<jats:sup>+<\/jats:sup>current was unaltered by either treatment. The enhanced inward and reduced outward currents also result in action potential prolongation after PMA or ET-1 pretreatment. We conclude that chronic PMA or ET-1 exposure in cultured NRVMs causes altered functional expression of cardiac ion currents, which mimic electrophysiological changes seen in whole animal and human hypertrophy and heart failure.<\/jats:p>","DOI":"10.1152\/ajpheart.00388.2010","type":"journal-article","created":{"date-parts":[[2010,12,4]],"date-time":"2010-12-04T05:38:48Z","timestamp":1291441128000},"page":"H617-H626","source":"Crossref","is-referenced-by-count":15,"title":["Phorbol ester and endothelin-1 alter functional expression of Na<sup>+<\/sup>\/Ca<sup>2+<\/sup>exchange, K<sup>+<\/sup>, and Ca<sup>2+<\/sup>currents in cultured neonatal rat myocytes"],"prefix":"10.1152","volume":"300","author":[{"given":"Jos\u00e9 L.","family":"Puglisi","sequence":"first","affiliation":[{"name":"Cardiovascular Institute and Departments of Medicine and Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; and"},{"name":"Departments of Pharmacology and Medicine, University of California Davis, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and Departments of Medicine and Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy","family":"Timofeyev","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, University of California Davis, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E.","family":"Myers","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, University of California Davis, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nipavan","family":"Chiamvimonvat","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, University of California Davis, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen M.","family":"Samarel","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and Departments of Medicine and Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and Departments of Medicine and Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois; and"},{"name":"Departments of Pharmacology and Medicine, University of California Davis, Davis, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.72.2.463"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.148288"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019807"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100455"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-010-0658-3"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.2.379"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(91)90135-9"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00545.2005"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/1357-2725(95)00142-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.3.384"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119755"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1139\/y95-242"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.62.2.347"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.05.016"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(90)90121-H"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91830-5"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.2.H577"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.2000.0758"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00544.2008"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00016.2003"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.10.017"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.1.209"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.2.262"},{"key":"B24","doi-asserted-by":"crossref","first-page":"10023","DOI":"10.1016\/S0021-9258(18)99178-7","volume":"266","author":"Kariya K","year":"1991","journal-title":"J Biol Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000012223.86441.A1"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1387.024"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.851"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(96)00366-4"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1042\/cs0870115"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019067"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113337"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.195313"},{"key":"B33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF00795386","volume":"87","author":"Long CS","year":"1992","journal-title":"Basic Res Cardiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.194035"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.15.1433"},{"key":"B36","doi-asserted-by":"crossref","first-page":"9466","DOI":"10.1016\/S0021-9258(17)36904-1","volume":"269","author":"McDonough PM","year":"1994","journal-title":"J Biol Chem"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1387.058"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1149"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.2.386"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00274-5"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39724"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117007"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp001"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114466"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.14.1802"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.11.1009"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1161\/hh1101.091193"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00461.2002"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.6.C2049"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1996.271.3.H1031"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1997.272.5.H2416"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.3.424"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.026468"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1991.261.4.H1067"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.96.1.195"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1139\/y05-120"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1387.059"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.4.1305"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.3.334"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.75.3.443"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00153-6"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.04.010"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1991.261.2.H364"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2006.04.025"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00171.2004"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.24.2455"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1126\/science.2845575"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1161\/hc3901.095766"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27374"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3221"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021418"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00388.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T17:56:37Z","timestamp":1636912597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00388.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2]]},"references-count":71,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,2]]}},"alternative-id":["10.1152\/ajpheart.00388.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00388.2010","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2]]}}}