Role of phospholamban in cyclic GMP mediated signaling in cardiac myocytes

Qihang Zhang, Peter M. Scholz, Anna Pilzak, Jun Su, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)157-166
Number of pages10
JournalCellular Physiology and Biochemistry
Volume20
Issue number1-4
DOIs
StatePublished - 2007

All Science Journal Classification (ASJC) codes

  • Physiology

Keywords

  • Cardiac myocyte function
  • Cyclic GMP
  • Natriuretic peptides
  • Nitric oxide
  • Phospholamban

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