Activity of cAMP-dependent Protein Kinase and Ca2+/calmodulin-dependent Protein Kinase in Failing and Nonfailing Human Hearts

Cardiovasc Res. 1999 Apr;42(1):254-61. doi: 10.1016/s0008-6363(98)00296-x.

Abstract

Objectives: A hallmark of human heart failure is prolonged myocardial relaxation. Although the intrinsic mechanism of phospholamban coupling to the Ca(2+)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Calcium-Calmodulin-Dependent Protein Kinases / analysis
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Case-Control Studies
  • Chromatography, Gel
  • Cyclic AMP-Dependent Protein Kinases / analysis
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Female
  • Heart Failure / enzymology*
  • Heart Failure / physiopathology
  • Hemodynamics
  • Humans
  • Male
  • Middle Aged
  • Myocardium / enzymology*
  • Regression Analysis

Substances

  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases