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Updated: May 6, 2026
Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice
Published on: September 17, 2015
Increased β-adrenergic inotropy in ventricular myocardium from Trpm4-/- mice
Ilka Mathar1, Miklos Kecskes, Gerry Van der Mieren
1From 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, Universität Heidelberg, Heidelberg, Germany (I.M., J.E.C.L., S.U., M.F.); and Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg, Germany (J.E.C.L., V.F., M.F.).
Rationale:
The Trpm4 gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca2+ -activated, but Ca2+ -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.
Objective:
To establish the role of TRPM4 in cardiac muscle function.
Methods And Results:
We used TRPM4 knockout mice and performed patch-clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure-volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca2+ -induced Ca2+ release. In Trpm4(-/-) mice, cardiac muscle displays an increased β-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 Trpm4(-/-) ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L-type Ca2+ current during the action potential, which explains the altered contractility of the heart muscle.
Conclusions:
Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of β-adrenergic stimulation on the ventricular heart muscle.
