CAMP CONCENTRATIONS, CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY, AND PHOSPHOLAMBAN IN NONFAILING AND FAILING MYOCARDIUM

Objective: Several signal transduction defects such as a reduction of myocardial cAMP formation and an altered intracellular Ca2+ handling h ave been observed in the failing human myocardium. The aim of the stud y was to obtain data on changes beyond cAMP formation involving cAMP d ependent protein kinase and its substrates. Methods: cAMP dependent pr otein kinase activity and cAMP concentrations were measured in the par ticulate and soluble fraction of failing human hearts (ischaemic, and dilated cardiomyopathy) and non-failing donor hearts. Phospholamban wa s quantified by cAMP dependent phosphorylation using P-32-ATP as subst rate and on western blots using a monoclonal antibody. Results: cAMP c oncentrations were reduced in the particulate fraction in both ischaem ic and dilated cardiomyopathy and in the soluble fraction in dilated c ardiomyopathy, but there was no difference in cAMP dependent protein k inase activity. Both phospholamban levels and cAMP dependent phosphory lation of phospholamban were similar in non-failing myocardium and in both ischaemic and dilated cardiomyopathy. Conclusions: These findings show that the reduction of cAMP formation is the predominant alterati on in heart failure, but cAMP dependent protein kinase and phospholamb an are evidently unchanged.