{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:09:38Z","timestamp":1790914178204,"version":"4.1.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2006,9,5]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Biological pacemakers (BPM) implanted in canine left bundle branch function competitively with electronic pacemakers (EPM). We hypothesized that BPM engineered with the use of mE324A mutant murine HCN2 (mHCN2) genes would improve function over mHCN2 and that BPM\/EPM tandems confer advantage over either approach alone.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            In cultured neonatal rat myocytes, activation midpoint was \u221246.9 mV in mE324A versus \u221266.1 mV in mHCN2 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). mE324A manifested a positive shift of voltage dependence of gating kinetics of activation and deactivation compared with mHCN2 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) in myocytes as well as\n            <jats:italic>Xenopus<\/jats:italic>\n            oocytes. In intact dogs in complete atrioventricular block, saline (control), mHCN2, or mE324A virus was injected into left bundle branch, and EPM were implanted (VVI 45 bpm). Twenty-four\u2013hour ECGs were monitored for 14 days. With EPM discontinued, there was no difference in duration of overdrive suppression among groups. However, basal heart rates in controls were less than those in mHCN2, which did not differ from those in E324A (45 versus 57 versus 53 bpm;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). When spontaneous rate fell below 45 bpm, EPM intervened at that rate, triggering 83% of beats in control, contrasting (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) with 26% (mHCN2) and 36% (mE324A). On day 14, epinephrine (1 \u03bcg\/kg per minute IV) induced a 50% heart rate increase in all mE324A, one third of mHCN2, and one fifth of control (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05 mE324A versus control or mHCN2).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            mE324A induces faster, more positive pacemaker current activation than mHCN2 and stable, catecholamine-sensitive rhythms in situ that compete with EPM comparably but more catecholamine responsively than mHCN2. BPM\/EPM tandems function reliably, reduce the number of EPM beats, and confer sympathetic responsiveness to the tandem.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.106.617613","type":"journal-article","created":{"date-parts":[[2006,8,22]],"date-time":"2006-08-22T00:13:41Z","timestamp":1156205621000},"page":"992-999","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["Wild-Type and Mutant HCN Channels in a Tandem Biological-Electronic Cardiac Pacemaker"],"prefix":"10.1161","volume":"114","author":[{"given":"Annalisa","family":"Bucchi","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei N.","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Shlapakova","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Peter","family":"Danilo","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Kryukova","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Qu","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongju","family":"Lu","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongming","family":"Pan","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Potapova","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce Ken","family":"Knight","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Girouard","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira S.","family":"Cohen","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Brink","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Robinson","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Rosen","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (A.B., A.N.P., I.S., P.D., Y.K., I.S.C., R.B.R., M.R.R.) and Pediatrics (M.R.R.), Center for Molecular Therapeutics, Columbia University, New York, NY; Guidant Corporation, St Paul, Minn (J.Q., B.K., S.G.); and Departments of Physiology and Biophysics, Institute of Molecular Cardiology, State University of New York at Stony Brook (Z.L., H.L., Z.P., I.P., I.S.C., P.R.B., M.R.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.05.012"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1330"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.86.5.559"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/419132b"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317959"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000059939.97249.2c"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000114527.10764.cc"},{"key":"e_1_3_2_8_2","first-page":"841","volume":"94","year":"2004","unstructured":"Potapova I, Plotnikov A, Lu Z, Danilo P Jr, Valiunas V, Qu J, Doronin S, Zuckerman J, Shlapakova IN, Gao J, Pan Z, Herron AJ, Robinson RB, Brink PR, Rosen MR, Cohen IS. Human mesenchymal stem cell as a gene delivery system to create cardiac pacemakers. Circ Res. 2004; 94: 841\u2013959.","journal-title":"Circ Res"},{"key":"e_1_3_2_9_2","first-page":"202","volume":"12","year":"2002","unstructured":"Biel M, Schneider A, Wahl C. Cardiac HCN channels: structure, function, and modulation. 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Elmsford NY: Pergamon Press; 1989: 1267\u20131329."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2004.12.016"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0276"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.106.617613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:29:59Z","timestamp":1715574599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.106.617613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,5]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2006,9,5]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.106.617613"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.106.617613","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,5]]},"assertion":[{"value":"2006-08-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}