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Cell Physiol Biochem ; 20(1-4): 157-66, 2007.
Article in English | MEDLINE | ID: mdl-17595525

ABSTRACT

We tested the hypothesis that the negative functional effects of cyclic GMP on cardiac myocytes were mediated through phospholamban (PLB) and activation of sarcoplasmic reticulum Ca(2+)-ATPase. Using ventricular myocytes from wild type (WT, n=10) and PLB knockout (PLB-KO, n=10) mouse hearts, functional changes were measured using a video edge detector at baseline and after 10(-6), 10(-5)M 8-bromo-cyclic GMP (cGMP), 10(-8), 10(-7)M C-type natriuretic peptide (CNP), or 10(-6), 10(-5)M S-nitroso-N-acetyl-penicillamine (SNAP, nitric oxide donor). Changes in cytosolic Ca(2+) concentration were assessed in fura 2-loaded WT and PLB-KO myocytes. Cyclic GMP dependent phosphorylation analysis was also performed in WT and PLB-KO myocytes. 8-bromo-cGMP 10(-5)M caused a significant decrease in %shortening (3.6+/-0.2% to 2.3+/-0.1%) in WT, but little change in PLB-KO myocytes (3.4+/-0.1% to 3.2+/-0.2%). Similarly, CNP and SNAP reduced %shortening of WT, but not PLB-KO myocyte. Changes in other contractile parameters such as maximum rate of shortening and relaxation were consistent with the changes in % shortening. Intracellular Ca(2+) transients changed similarly to cell contractility in WT and PLB-KO myocytes treated with cGMP and CNP; i.e. Ca(2+) transients decreased with cGMP or CNP in WT myocytes, but were unchanged in PLB-KO myocytes. cGMP dependent phosphorylation analysis showed that some proteins were phosphorylated by cGMP to a lesser extent in PLB-KO compared with WT myocytes, suggesting impaired cGMP-kinase function in PLB-KO cardiac myocytes. These results indicated that cGMP-induced reductions in cardiac myocyte function were at least partially mediated through the action of phospholamban.


Subject(s)
Calcium-Binding Proteins/metabolism , Cyclic GMP/metabolism , Myocytes, Cardiac/metabolism , Animals , Calcium Signaling/drug effects , Calcium-Binding Proteins/deficiency , Calcium-Binding Proteins/genetics , Cyclic GMP/analogs & derivatives , Cyclic GMP/pharmacology , Female , In Vitro Techniques , Male , Mice , Mice, Knockout , Myocardial Contraction/drug effects , Myocardial Contraction/physiology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Natriuretic Peptide, C-Type/pharmacology , Nitric Oxide Donors/pharmacology , Phosphorylation , S-Nitroso-N-Acetylpenicillamine/pharmacology , Signal Transduction/drug effects
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