© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts
aInstitut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität, Domagkstrasse 12, D-48149 Münster, Germany
bAbteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
* Corresponding author. Tel.: +49-2518-3555-10; fax: +49-2518-3555-01.
Objectives: A hallmark of human heart failure is prolonged myocardial relaxation. Although the intrinsic mechanism of phospholamban coupling to the Ca2+-ATPase is unaltered in normal and failed human hearts, it remains possible that regulation of phospholamban phosphorylation by cAMP-dependent mechanisms or other second messenger pathways could be perturbed, which may account partially for the observed dysfunctions of the sarcoplasmic reticulum (SR) associated with this disease. Methods: cAMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaM kinase) were characterized initially by DEAE-Sepharose chromatography in hearts from patients with end-stage dilated cardiomyopathy. We measured the activity of PKA and CaM kinase in left ventricular tissue of failing (idiopathic dilated cardiomyopathy; ischemic heart disease) and nonfailing human hearts. Results: Basal PKA activity was not changed between failing and nonfailing hearts. One major peak of CaM kinase activity was detected by DEAE-Sepharose chromatography. CaM kinase activity was increased almost 3-fold in idiopathic dilated cardiomyopathy. In addition, hemodynamical data (left ventricular ejection fraction, cardiac index) from patients suffering from IDC positively correlate with CaM kinase activity. Conclusions: Increased CaM kinase activity in hearts from patients with dilated cardiomyopathy could play a role in the abnormal Ca2+ handling of the SR and heart muscle cell.
KEYWORDS cAMP-dependent protein kinase; Ca2+/calmodulin-dependent protein kinase II; Heart failure
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