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SERCA inhibition limits the functional effects of cyclic GMP in both control and hypertrophic cardiac myocytes

Qihang Zhang1, Tomer Davidov, Harvey R Weiss

  • 1Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08903-0019, USA.

Pharmacology
|March 5, 2009
PubMed

Insights

In cardiac hypertrophy, cyclic GMP

Area of Science:

  • Cardiovascular Physiology
  • Cellular Biology

Background:

  • Cyclic GMP (cGMP) normally regulates cardiac myocyte function.
  • In cardiac hypertrophy, the effects of cGMP are diminished.
  • The sarcoplasmic reticulum calcium-ATPase (SERCA) is implicated in cGMP signaling.

Purpose of the Study:

  • To investigate the hypothesis that the interaction between cGMP and SERCA is reduced in hypertrophic cardiac myocytes.
  • To determine if SERCA activity influences the blunted response to cGMP in hypertrophy.

Main Methods:

  • Myocytes were isolated from control and hypertrophic rabbits.
  • Cells were treated with 8-bromo-cGMP (8-Br-cGMP) alone or after SERCA inhibition with thapsigargin or cyclopiazonic acid (CPA).
  • Myocyte shortening, relaxation, and intracellular calcium transients were measured.

Main Results:

  • 8-Br-cGMP significantly decreased shortening in control myocytes but had a smaller effect in hypertrophic myocytes.
  • SERCA inhibition blunted the effects of 8-Br-cGMP in control myocytes.
  • In hypertrophic myocytes, SERCA inhibition abolished the response to 8-Br-cGMP.
  • Intracellular calcium dynamics mirrored functional changes.

Conclusions:

  • The blunted response to cGMP in hypertrophic myocytes is not directly related to SERCA.
  • SERCA inhibition affects cGMP responses in both control and hypertrophic myocytes, suggesting complex interactions.

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