{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:34:00Z","timestamp":1780666440932,"version":"3.54.1"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,8,14]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Rationale:<\/jats:italic>\n            <\/jats:bold>\n            The cardiac inwardly rectifying K\n            <jats:sup>+<\/jats:sup>\n            current (\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>K1<\/jats:sub>\n            ) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Objective:<\/jats:italic>\n            <\/jats:bold>\n            This study aims to analyze the effects of nitric oxide (NO) on human atrial\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>K1<\/jats:sub>\n            and on Kir2.1 channels, the major isoform of inwardly rectifying channels present in the human heart.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results:<\/jats:italic>\n            <\/jats:bold>\n            Currents were recorded in enzymatically isolated myocytes and in transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 to 500 nmol\/L) increased inward and outward\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>K1<\/jats:sub>\n            and\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Kir2.1<\/jats:sub>\n            . These effects were accompanied by hyperpolarization of the resting membrane potential and a shortening of the duration of phase 3 of the human atrial action potential. The\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>Kir2.1<\/jats:sub>\n            increase was attributable to an increase in the open probability of the channel. Site-directed mutagenesis analysis demonstrated that NO effects were mediated by the selective\n            <jats:italic>S<\/jats:italic>\n            -nitrosylation of Kir2.1 Cys76 residue. Single ion monitoring experiments performed by liquid chromatography\/tandem mass spectrometry suggested that the primary sequence that surrounds Cys76 determines its selective\n            <jats:italic>S<\/jats:italic>\n            -nitrosylation. Chronic atrial fibrillation, which produces a decrease in NO bioavailability, decreased the\n            <jats:italic>S<\/jats:italic>\n            -nitrosylation of Kir2.1 channels in human atrial samples as demonstrated by a biotin-switch assay, followed by Western blot.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions:<\/jats:italic>\n            <\/jats:bold>\n            The results demonstrated that, under physiological conditions, NO regulates human cardiac\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>K1<\/jats:sub>\n            through a redox-related process.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.197558","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T02:07:39Z","timestamp":1247796459000},"page":"383-392","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Nitric Oxide Increases Cardiac\n            <i>I<\/i>\n            <sub>K1<\/sub>\n            by Nitrosylation of Cysteine 76 of Kir2.1 Channels"],"prefix":"10.1161","volume":"105","author":[{"given":"Ricardo","family":"Go\u0301mez","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Caballero","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Barana","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Amoro\u0301s","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Calvo","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Lo\u0301pez","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Klein","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Vaquero","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Osuna","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Atienza","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesu\u0301s","family":"Almendral","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u0301ngel","family":"Pinto","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tamargo","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Delpo\u0301n","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology (R.G., R.C., A.B., I.A., M.V., L.O., J.T., E.D.), School of Medicine, Universidad Complutense, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (E.C., J.A.L.), Madrid, Spain; Department of Physiology, Montreal University (H.K.), Canada; and Hospital General Universitario Gregorio Maran\u0303o\u0301n (F.A., J.A., A.P.), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1344"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2004.11.012"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.98.22.2422"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126714"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61307-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.121475"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.04.005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn205"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.06.021"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.04.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1569"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)75100-5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80711-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000183735.09871.61"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.21.2551"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085028"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.05.010"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.108.136721"},{"key":"e_1_3_3_19_2","first-page":"13i","volume":"96","year":"2005","unstructured":"Malinski T. 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