Increased basal contractility of cardiomyocytes overexpressing protein kinase Cε and blunted positive inotropic response to endothelin-1

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Abstract
Objective: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation–contraction coupling process by vasoactive peptides like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. Methods: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKCϵ in cultured adult rabbit ventricular myocytes (Ad-PKCϵ). Myocyte shortening and [Ca2+]i transients under basal and ET-1-stimulated conditions were measured in Ad-PKCϵ and Ad-LacZ control transfected cells. Results: Infection with Ad-PKCϵ resulted in a strong, virus dose-dependent increase in PKCϵ protein levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKCϵ kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+]i transient amplitude were both increased by 21% (PConclusion: Specific overexpression of PKCϵ in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+]i transients, and modifies their responsiveness to ET-1.

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