Increased β-adrenergic inotropy in ventricular myocardium from trpm4-/- mice. (LB666)

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 Ca(2+)-activated, but Ca(2+)-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 Ca(2+)-induced Ca(2+) 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...