{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:49:57Z","timestamp":1792730997151,"version":"4.5.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,12,10]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              The rapid delayed rectifier potassium current,\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              , which flows through the human ether-a-go-go-related (hERG) channel, is a major determinant of the shape and duration of the human cardiac action potential (APD). However, it is unknown whether the time dependency of\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              enables it to control APD, conduction velocity (CV), and wavelength (WL) at the exceedingly high activation frequencies that are relevant to cardiac reentry and fibrillation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To test the hypothesis that upregulation of hERG increases functional reentry frequency and contributes to its stability.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Using optical mapping, we investigated the effects of\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              upregulation on reentry frequency, APD, CV, and WL in neonatal rat ventricular myocyte (NRVM) monolayers infected with GFP (control), hERG (\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              ), or dominant negative mutant hERG G628S. Reentry frequency was higher in the\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              -infected monolayers (21.12\u00b10.8 Hz; n=43 versus 9.21\u00b10.58 Hz; n=16;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) but slightly reduced in G628S-infected monolayers. APD\n              <jats:sub>80<\/jats:sub>\n              in the\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              -infected monolayers was shorter (&gt;50%) than control during pacing at 1 to 5 Hz. CV was similar in both groups at low frequency pacing. In contrast, during high-frequency reentry, the CV measured at varying distances from the center of rotation was significantly faster in\n              <jats:italic>I<\/jats:italic>\n              <jats:sub>Kr<\/jats:sub>\n              -infected monolayers than controls. Simulations using a modified NRVM model predicted that rotor acceleration was attributable, in part, to a transient hyperpolarization immediately following the AP. The transient hyperpolarization was confirmed experimentally.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>hERG overexpression dramatically accelerates reentry frequency in NRVM monolayers. Both APD and WL shortening, together with transient hyperpolarization, underlies the increased rotor frequency and stability.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.110.232470","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T02:55:51Z","timestamp":1287111351000},"page":"1503-1511","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["A Major Role for hERG in Determining Frequency of Reentry in Neonatal Rat Ventricular Myocyte Monolayer"],"prefix":"10.1161","volume":"107","author":[{"given":"Luqia","family":"Hou","sequence":"first","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makarand","family":"Deo","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Furspan","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep V.","family":"Pandit","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Mironov","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Auerbach","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuming","family":"Gong","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Berenfeld","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jalife","sequence":"additional","affiliation":[{"name":"From the Center for Arrhythmia Research (L.H., M.D., P.F., S.V.P., S.M., D.S.A., O.B., J.J.) and Department of Molecular and Integrative Physiology (L.H., J.J.), University of Michigan, Ann Arbor; Department of Pharmacology (D.S.A.), State University of New York Upstate Medical University, Syracuse; and Division of Cardiovascular Medicine (Q.G., Z.Z.), Oregon Health and Science University, Portland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.62.1.25"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709758104"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/9781444316940"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.121475"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.149617"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04710"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2008.05.009"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2008.10.006"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000109482.92774.3A"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.708818"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000022854.95998.5c"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.737254"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2008.10.026"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001860403"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.10.929"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh2401.100818"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.08.005"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.8.3438"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000085071.28695.C4"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.325"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1317"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1377"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.1.26"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2007.05.021"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.110.232470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:09:01Z","timestamp":1715573341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.110.232470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,10]]},"references-count":24,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2010,12,10]]}},"alternative-id":["10.1161\/CIRCRESAHA.110.232470"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.110.232470","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12,10]]},"assertion":[{"value":"2010-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}