Cardiac specific overexpression of Gαq alters excitation-contraction coupling in isolated cardiac myocytes

Atsuko Yatani, Konrad Frank, Hidenori Sako, Evangelia G. Kranias, Gerald W. Dorn

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35 Scopus citations


Transgenic mice with cardiac-specific overexpression of Gαq exhibit a biochemical and physiological phenotype of load-independent cardiac hypertrophy with contractile dysfunction. To elucidate the cellular basis for altered contractility, we measured cellular contraction, Ca2+ transients, and L-type Ca2+ channel currents (I(Ca) in left ventricular (LV) myocytes isolated from non transgenic (NT) controls or Gαq hearts. Although baseline contractile function (% shortening) and the amplitude of Ca2+ transients in Gαq myocytes were similar to NT myocytes, the rates of cellular shortening and relengthening and the duration of Ca2+ transients were prolonged in Gαq myocytes. Myocytes from Gαq hearts had larger cell capacitance but no change in I(Ca) density, voltage-dependence of activation and inactivation. The responses of I(Ca) to dihydropyridine drugs and a membrane permeable cAMP analog, 8-(4-chlorophenylthio) cAMP, were not altered; however, the time course of I(Ca) inactivation was significantly slower in Gαq myocytes compared to NT myocytes. The kinetic difference in inactivation was abolished when Ba2+ was used as the charge carrier or when the sarcoplasmic reticulum (SR) Ca2+ was depleted by ryanodine, suggesting that Ca2+-dependent inactivation is reduced in Gαq myocytes due to altered SR Ca2+ release. Consistent with this hypothesis, the function of SR as assessed by the maximal Ca2+ uptake rates and the apparent affinity of SR Ca2+-ATPase for Ca2+ was reduced in ventricles of Gαq heart. These results suggest that the reduced SR function contributes to the depressed contractility associated with this form of cardiac hypertrophy.

Original languageEnglish
Pages (from-to)1327-1336
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Issue number7
StatePublished - Jul 1999


  • Heart failure
  • L-type Ca channels
  • Patch clamp
  • Sarcoplasmic reticulum
  • Transgenic mice


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