{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:52:37Z","timestamp":1778547157674,"version":"3.51.4"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              Intracellular pH (pH\n              <jats:sub>i<\/jats:sub>\n              ) is critical to cardiac excitation and contraction; uncompensated changes in pH\n              <jats:sub>i<\/jats:sub>\n              impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH\n              <jats:sub>i<\/jats:sub>\n              regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl\n              <jats:sup>\u2212<\/jats:sup>\n              \/HCO\n              <jats:sub>3<\/jats:sub>\n              <jats:sup>\u2212<\/jats:sup>\n              exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH\n              <jats:sub>i<\/jats:sub>\n              , but also cardiac excitability.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>\n              To test the mechanistic role of Slc26a6 in the heart, we took advantage of\n              <jats:italic>Slc26a6<\/jats:italic>\n              knockout (\n              <jats:italic>Slc26a6<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/<\/jats:italic>\n              <\/jats:sup>\n              <jats:sup>\n                <jats:italic>\u2212<\/jats:italic>\n              <\/jats:sup>\n              ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of\n              <jats:italic>Slc26a6<\/jats:italic>\n              results in action potential shortening. There are reduced Ca\n              <jats:sup>2+<\/jats:sup>\n              transient and sarcoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              load, together with decreased sarcomere shortening in\n              <jats:italic>Slc26a6<\/jats:italic>\n              <jats:sup>\u2212\/<\/jats:sup>\n              <jats:sup>\u2212<\/jats:sup>\n              cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH\n              <jats:sub>i<\/jats:sub>\n              is elevated in\n              <jats:italic>Slc26a6<\/jats:italic>\n              <jats:sup>\u2212\/<\/jats:sup>\n              <jats:sup>\u2212<\/jats:sup>\n              cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl\n              <jats:sup>\u2212<\/jats:sup>\n              \/HCO\n              <jats:sub>3<\/jats:sub>\n              <jats:sup>\u2212<\/jats:sup>\n              exchange activities of Slc26a6. Moreover,\n              <jats:italic>Slc26a6<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/<\/jats:italic>\n              <\/jats:sup>\n              <jats:sup>\n                <jats:italic>\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl\n              <jats:sup>\u2212<\/jats:sup>\n              \/HCO\n              <jats:sub>3<\/jats:sub>\n              <jats:sup>\u2212<\/jats:sup>\n              transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH\n              <jats:sub>i<\/jats:sub>\n              , excitability, and contractility. pH\n              <jats:sub>i<\/jats:sub>\n              is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in\n              <jats:italic>Slc26a6<\/jats:italic>\n              <jats:sup>\u2212\/<\/jats:sup>\n              <jats:sup>\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.117.005267","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:10:28Z","timestamp":1507853428000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Action Potential Shortening and Impairment of Cardiac Function by Ablation of\n            <i>Slc26a6<\/i>"],"prefix":"10.1161","volume":"10","author":[{"given":"Padmini","family":"Sirish","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah A.","family":"Ledford","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy","family":"Timofeyev","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phung N.","family":"Thai","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ren","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seojin","family":"Park","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong Han","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu","family":"Dai","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Moshref","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Choong-Ryoul","family":"Sihn","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Valeryevna","family":"Timofeyeva","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Jian","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno (J.H.L., E.N.Y.); and Department of Veterans..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Shimkunas","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Department of Internal Medicine (P.S., H.A.L., V.T., P.N.T., L.R., S.P., G.D., M.M., C.-R.S., W.C.C., M.V.T., N.C., Y.C.-I., X.-D.Z.), Center for Neuroscience (H.J.K.), Department of Pharmacology (Z.J., R.S., L.T.I., N.C., Y.C.-I.) and Department of Biomedical Engineering (R.S., Y.C.-I.), University of California, Davis; 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