Modulation of cardiac contractility by serine/threonine protein phosphatase type 5

Gergs Ulrich, Boknik Peter, Buchwalow IgorB, Fabritz Larissa, Gruendker Nicole, Kucerova Dana, Matus Marek, Werner Franziska, Schmitz Wilhelm, Neumann Joachim

Abstract

Background: Protein phosphatase 5 (PP5) a serine/threonine phosphatase is ubiquitously expressed in mammalian tissues including the heart, but its physiological role in the heart is still unknown. Therefore, we used a transgenic mouse model to get a first insight into the cardiac role of PP5. Methods and results: We generated transgenic mice with cardiac myocyte specific overexpression of PP5. Successful overexpression of PP5 was demonstrated by Western blotting, immunohistochemistry and enhanced arachidonic acid-stimulated protein phosphatase activity in transgenic hearts. Cardiac function was examined on the level of isolated cardiac myocytes, isolated organs and in intact animals. Whereas Ca(2+) transients and cell shortening remained unchanged, L-type Ca(2+) currents were decreased in isolated cardiac myocytes from transgenic mice. Ventricular contractility was reduced in isolated perfused hearts under basal conditions and after beta-adrenergic stimulation. In intact animals, echocardiography revealed increased left ventricular diameters and decreased contractility and invasively measured hemodynamic performance by left ventricular catheterization demonstrated a reduced response to beta-adrenergic stimulation in transgenic mice compared to wild type. Conclusions: Overexpression of PP5 affected contractility and beta-adrenergic signaling in the hearts of transgenic mice. Taken together, these findings are indicative of a regulatory role of PP5 in cardiac function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.