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Abnormal contraction caused by expression of G(i)-coupled receptor in transgenic model of dilated cardiomyopathy

A J Baker1, C H Redfern, M D Harwood

  • 1Department of Radiology, University of California, San Francisco, California 94143, USA. ajbaker@itsa.ucsf.edu

American Journal of Physiology. Heart and Circulatory Physiology
|March 15, 2001
PubMed

Insights

Increased G(i) signaling impairs heart muscle contractility, potentially contributing to dilated cardiomyopathy. This study used genetically modified mice to investigate these effects on myocardial function.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Physiology

Background:

  • Increased G(i) signaling is linked to dilated cardiomyopathy in humans.
  • The precise role of G(i) signaling in myocardial function remains unclear.

Purpose of the Study:

  • To investigate the effects of chronically increased G(i) signaling on myocardial function.
  • To determine the impact of G(i) signaling on cardiac contractility and relaxation.

Main Methods:

  • Utilized transgenic mice expressing a heart-targeted, tetracycline-controlled G(i)-coupled receptor (Ro1).
  • Assessed myocardial function, including force generation, calcium sensitivity, and contraction/relaxation kinetics, in Ro1-expressing and control mice.

Main Results:

  • Ro1 expression significantly reduced myocardial force (>60%) and slowed contraction/relaxation kinetics.
  • Enhanced sensitivity to extracellular calcium was observed with Ro1 expression.
  • Ro1-expressing myocardium showed impaired force response to increased pacing frequency and post-rest decay.

Conclusions:

  • Chronic elevation of G(i) signaling leads to significant defects in cardiac contractility.
  • These findings suggest that impaired contractility mediated by G(i) signaling may contribute to the pathogenesis of dilated cardiomyopathy.

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