{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:18:31Z","timestamp":1791191911408,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,1,17]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>\n              The\n              <jats:italic>Trpm4<\/jats:italic>\n              gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca\n              <jats:sup>2+<\/jats:sup>\n              -activated, but Ca\n              <jats:sup>2+<\/jats:sup>\n              -impermeable, nonselective cation channels and are expressed both in atrial and in ventricular cardiomyocytes. The physiological function of TRPM4 in the heart remains, however, incompletely understood.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>To establish the role of TRPM4 in cardiac muscle function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>\n              We used TRPM4 knockout mice and performed patch-clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure\u2013volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca\n              <jats:sup>2+<\/jats:sup>\n              -induced Ca\n              <jats:sup>2+<\/jats:sup>\n              release. In\n              <jats:italic>Trpm4<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, cardiac muscle displays an increased \u03b2-adrenergic inotropic response both in vitro and in vivo. Measurements of action potential duration show a significantly decreased time for 50% and 90% repolarization in\n              <jats:italic>Trpm4<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L-type Ca\n              <jats:sup>2+<\/jats:sup>\n              current during the action potential, which explains the altered contractility of the heart muscle.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of \u03b2-adrenergic stimulation on the ventricular heart muscle.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.114.302835","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T06:09:52Z","timestamp":1384409392000},"page":"283-294","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["Increased \u03b2-Adrenergic Inotropy in Ventricular Myocardium From\n            <i>Trpm4<\/i>\n            <sup>\u2212\/\u2212<\/sup>\n            Mice"],"prefix":"10.1161","volume":"114","author":[{"given":"Ilka","family":"Mathar","sequence":"first","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miklos","family":"Kecskes","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry","family":"Van der Mieren","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griet","family":"Jacobs","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan E.","family":"Camacho Londo\u00f1o","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Uhl","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Flockerzi","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Voets","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Freichel","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Nilius","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Herijgers","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., P.H.); Pharmakologisches Institut, Universit\u00e4t Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universit\u00e4t des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Vennekens","sequence":"additional","affiliation":[{"name":"From the Department of Molecular and Cellular Medicine, Laboratory of Ion Channel Research, Leuven, Belgium (I.M., M.K., G.J., T.V., B.N., R.V.); Research Unit of Experimental Cardiac Surgery, KU Leuven, Leuven, Belgium (G.V.d.M., 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