Cyclic GMP signaling and regulation of SERCA activity during cardiac myocyte contraction

Qihang Zhang, Peter M. Scholz, Yiqi He, James Tse, Harvey R. Weiss

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

We tested the hypothesis that cGMP-induced reductions in cardiac myocyte function were related to activation of the sarcoplasmic reticulum Ca2+-ATPase (SERCA) and cGMP-dependent phosphorylation of phospholamban. Ventricular myocyte function was measured using a video edge detector (n = 11 rabbits). Thapsigargin (TG) or cyclopiazonic acid (CPA) were used to inhibit SERCA. 8-Bromo-cGMP was added at 10-6, 10-5 M followed by TG 10-8 M or KT5823 (cGMP-protein kinase inhibitor, 10-6 M) prior to TG or CPA. Cyclic GMP-dependent protein phosphorylation and immunoblotting with anti-phospholamban antibody were examined. TG 10-8 M significantly increased percent shortening (from 6.6 ± 0.7 to 9.1 ± 1.3%). Cyclic GMP 10-5 M significantly decreased cell shortening from 9.3 ± 0.9 to 5.1 ± 0.6%. This was partially reversed by KT5823 (5.1 ± 0.6 to 8.2 ± 1.4%) suggesting that negative functional effects of cGMP were partially through the cGMP-dependent protein kinase. Addition of TG after cGMP also reduced the negative effects of cGMP on myocyte shortening suggesting involvement of SERCA in cGMP signaling. TG after cGMP and KT5823 treatment did not alter myocyte contractility (8.2 ± 1.4 to 7.2 ± 1.3%). CPA had similar effects as those of TG. Protein phosphorylation and immunoblotting showed that phospholamban was a target of the cGMP protein kinase. These results indicated that the cyclic GMP-induced reductions in myocyte function were partially mediated through the action of SERCA. It further suggested that cGMP signaling affects myocyte function through phosphorylation of phospholamban which regulates SERCA activity.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalCell Calcium
Volume37
Issue number3
DOIs
StatePublished - Mar 2005

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Keywords

  • Cyclic GMP
  • Cyclic GMP protein kinase
  • Phospholamban
  • Phosphorylation
  • Rabbit
  • SERCA

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