RGS4 reduces contractile dysfunction and hypertrophic gene induction in Galpha q overexpressing mice

J Mol Cell Cardiol. 2001 Feb;33(2):209-18. doi: 10.1006/jmcc.2000.1307.


The intrinsic GTPase activity of Galpha q is low, and RGS proteins which activate GTPase are expressed in the heart; however, their functional relevance in vivo is unknown. Transgenic mice with cardiac-specific overexpression of Galpha q in myocardium exhibit cardiac hypertrophy, enhanced PKC xi membrane translocation, embryonic gene expression, and depressed cardiac contractility. We recently reported that transgenic mice with cardiac-specific expression of RGS4, a Galpha q and Galpha i GTPase activator, exhibit decreased left ventricular hypertrophy and ANF induction in response to pressure overload. To test the hypothesis that RGS4 can act as a Galpha q-specific GTPase activating protein (GAP) in the in vivo heart, dual transgenic Galpha q-40xRGS4 mice were generated to determine if RGS4 co-expression would ameliorate the Galpha q-40 phenotype. At age 4 weeks, percent fractional shortening was normalized in dual transgenic mice as was left ventricular internal dimension and posterior and septal wall thicknesses. PKC xi membrane translocation and ANF and alpha -skeletal actin mRNA levels were also normalized. Compound transgenic mice eventually developed depressed cardiac contractility that was evident by 9 weeks of age. These studies establish for the first time a role for RGS4 as a GAP for Galpha q in the in vivo heart, and demonstrate that its regulated expression can have pathophysiologic consequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Atrial Natriuretic Factor / metabolism
  • Blotting, Northern
  • Blotting, Western
  • Cardiomegaly / genetics*
  • Cell Nucleus / metabolism
  • Echocardiography
  • GTPase-Activating Proteins / metabolism
  • Isoenzymes / metabolism
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Myocardial Contraction / physiology*
  • Phenotype
  • Protein Kinase C / metabolism
  • Protein Kinase C-epsilon
  • Protein Transport
  • RGS Proteins / metabolism*
  • RGS Proteins / physiology*
  • RNA, Messenger / metabolism
  • Time Factors


  • Actins
  • GTPase-Activating Proteins
  • Isoenzymes
  • RGS Proteins
  • RNA, Messenger
  • RGS4 protein
  • Atrial Natriuretic Factor
  • Prkce protein, mouse
  • Protein Kinase C
  • Protein Kinase C-epsilon