cAMP concentrations, cAMP dependent protein kinase activity, and phospholamban in non-failing and failing myocardium

Abstract

Objective: Several signal transduction defects such as a reduction of myocardial cAMP formation and an altered intracellular Ca²⁺ handling have been observed in the failing human myocardium. The aim of the study was to obtain data on changes beyond cAMP formation involving cAMP dependent protein kinase and its substrates. Methods: cAMP dependent protein kinase activity and cAMP concentrations were measured in the particulate and soluble fraction of failing human hearts (ischaemic, and dilated cardiomyopathy) and non-failing donor hearts. Phospholamban was quantified by cAMP dependent phosphorylation using ³²P-ATP as substrate and on western blots using a monoclonal antibody. Results: cAMP concentrations were reduced in the particulate fraction in both ischaemic and dilated cardiomyopathy and in the soluble fraction in dilated cardiomyopathy, but there was no difference in cAMP dependent protein kinase activity. Both phospholamban levels and cAMP dependent phosphorylation of phospholamban were similar in non-failing myocaidium and in both ischaemic and dilated cardiomyopathy. Conclusions: These findings show that the reduction of cAMP formation is the predominant alteration in heart failure, but cAMP dependent protein kinase and phospholamban are evidently unchanged. Cardiovascular Research 1994;28:1713-1719