Cyclic GMP-induced reduction in cardiac myocyte function is partially mediated by activation of the sarcoplasmic reticulum Ca2+-ATPase

Qihang Zhang, Lin Yan, Harvey R. Weiss, Peter M. Scholz

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21 Scopus citations

Abstract

We tested the hypothesis that the mechanism through which cyclic GMP reduces cardiac function is mediated by activation of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Cardiac myocytes were isolated from New Zealand white rabbits (n = 11). Individual ventricular cells were stimulated by electrical field stimulation. The maximal rate of cell shortening and percentage shortening were measured with a video edge detector. Thapsigargin (10-8 mol/l) was used as a specific inhibitor of SERCA. When 8-bromo-cyclic GMP (8-Br-cGMP, 10-7, -6, -5 mol/l) was added to cells, the maximal rate of myocyte shortening (Rmax, μm/s) and percentage shortening were both decreased in a concentration-dependent manner. Rmax decreased 27% from 117 ± 12 at baseline to 85.2 ± 13 when 10-5 mol/l of 8-Br-cGMP was present, and percent shortening was reduced 28% from 6.0 ± 0.5 to 4.3 ± 0.5%. Thapsigargin (10-8 mol/l) increased the maximal rate of myocyte shortening and percent shortening. Addition of thapsigargin prior to 8-Br-cGMP reduced the negative effects of cGMP on myocyte function. The percent shortening decreased only 11% and Rmax decreased 14% with 10-5 mol/l 8-Br-cGMP, which was not significant. Cyclopiazonic acid, another SERCA inhibitor, was also used to test whether 8-Br-cGMP reduced myocyte function through SERCA. The results were similar to those when thapsigargin was used. These results indicated that the cyclic GMP-induced reduction in cardiac myocyte function was partially mediated through the action of the sarcoplasmic reticulum Ca2+-ATPase.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalPharmacology
Volume64
Issue number2
DOIs
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Ca-ATPase
  • Cyclic GMP
  • Myocyte shortening
  • Rabbit
  • Thapsigargin

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