{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:25:38Z","timestamp":1791080738763,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,10,9]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Rationale<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Mutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na\n                    <jats:sup>+<\/jats:sup>\n                    current (\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    ) and cause Brugada Syndrome (BrS). GPD1-L has &gt;80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in NAD-dependent energy metabolism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Objective<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Therefore, we tested whether NAD(H) could regulate human cardiac sodium channels (Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Methods and Results<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    HEK293 cells stably expressing Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 and rat neonatal cardiomyocytes were used. The influence of NADH\/NAD\n                    <jats:sup>+<\/jats:sup>\n                    on arrhythmic risk was evaluated in wild-type or SCN5A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mouse heart. A280V GPD1-L caused a 2.48\u00b10.17-fold increase in intracellular NADH level (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). NADH application or cotransfection with A280V GPD1-L resulted in decreased\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    (0.48\u00b10.09 or 0.19\u00b10.04 of control group, respectively;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01), which was reversed by NAD\n                    <jats:sup>+<\/jats:sup>\n                    , chelerythrine, or superoxide dismutase. NAD\n                    <jats:sup>+<\/jats:sup>\n                    antagonism of the Na\n                    <jats:sup>+<\/jats:sup>\n                    channel downregulation by A280V GPD1-L or NADH was prevented by a protein kinase (PK)A inhibitor, PKAI\n                    <jats:sub>6\u201322<\/jats:sub>\n                    . The effects of NADH and NAD\n                    <jats:sup>+<\/jats:sup>\n                    were mimicked by a phorbol ester and forskolin, respectively. Increasing intracellular NADH was associated with an increased risk of ventricular tachycardia in wild-type mouse hearts. Extracellular application of NAD\n                    <jats:sup>+<\/jats:sup>\n                    to SCN5A\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mouse hearts ameliorated the risk of ventricular tachycardia.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Conclusions<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Our results show that Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 is regulated by pyridine nucleotides, suggesting a link between metabolism and\n                    <jats:italic>I<\/jats:italic>\n                    <jats:sub>Na<\/jats:sub>\n                    . This effect required protein kinase C activation and was mediated by oxidative stress. NAD\n                    <jats:sup>+<\/jats:sup>\n                    could prevent this effect by activating PKA. Mutations of GPD1-L may downregulate Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 by altering the oxidized to reduced NAD(H) balance.\n                  <\/jats:p>","DOI":"10.1161\/circresaha.109.197277","type":"journal-article","created":{"date-parts":[[2009,9,10]],"date-time":"2009-09-10T21:44:56Z","timestamp":1252619096000},"page":"737-745","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":118,"title":["Cardiac Na\n                    <sup>+<\/sup>\n                    Current Regulation by Pyridine Nucleotides"],"prefix":"10.1161","volume":"105","author":[{"given":"Man","family":"Liu","sequence":"first","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamarendra","family":"Sanyal","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman S.","family":"Gurung","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Gaconnet","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie J.","family":"Kerchner","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan L.","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.-H.","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Grace","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"London","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Samuel C.","family":"Dudley","sequence":"additional","affiliation":[{"name":"From the Division in Cardiology (M.L., G. Gao, G. Gaconnet, L.L.S., S.C.D.), University of Illinois at Chicago and the Jesse Brown Veteran Affairs Medical Center, Ill; Department of Medicine (S.S.), Pulmonary Division, Duke University, Durham, NC; Department of Biochemistry (I.S.G., C.L.-H.H., A.G.), University of Cambridge, United Kingdom; and the Cardiovascular Institute (X.Z., L.J.K., B.L.), University of Pittsburgh, Pa."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90253-J"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2005.01496.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.88.12.e78"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/hh0102.102977"},{"key":"e_1_3_3_5_2","first-page":"425","volume":"20","year":"2004","unstructured":"Baroudi G, Napolitano C, Priori SG, Del Bufalo A, Chahine M. 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