Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active Gαo* protein

Ming Zhu, Agnieszka A. Gach, Gong Xin Liu, Xiaomei Xu, Chew Lim Chee, Julie X. Zhang, Lan Mao, Kurt Chuprun, Walter J. Koch, Ronglih Liao, Gideon Koren, Burns C. Blaxall, Ulrike Mende

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of Go is still poorly defined. To investigate the role of Gαo in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of Gαo1* (Gαo*), the predominant Gαo isoform in the heart. Gαo expression was increased 3- to 15-fold in mice from 5 independent lines, all of which had a normal life span and no gross cardiac morphological abnormalities. We demonstrate enhanced contractile function in Gαo* transgenic mice in vivo, along with increased L-type Ca2+ channel current density, calcium transients, and cell shortening in ventricular Gαo*-expressing myocytes compared with wild-type controls. These changes were evident at baseline and maintained after isoproterenol stimulation. Expression levels of all major Ca2+ handling proteins were largely unchanged, except for a modest reduction in Na+/Ca2+ exchanger in transgenic ventricles. In contrast, phosphorylation of the ryanodine receptor and phospholamban at known PKA sites was increased 1.6- and 1.9-fold, respectively, in Gαo* ventricles. Density and affinity of β-adrenoceptors, cAMP levels, and PKA activity were comparable in Gαo* and wild-type myocytes, but protein phosphatase 1 activity was reduced upon Gαo* expression, particularly in the vicinity of the ryanodine receptor. We conclude that Gαo* exerts a positive effect on Ca2+ cycling and contractile function. Alterations in protein phosphatase 1 activity rather than PKA-mediated phosphorylation might be involved in hyperphosphorylation of key Ca2+ handling proteins in hearts with constitutive Gαo activation.

Original languageEnglish
Pages (from-to)H1335-H1347
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3
StatePublished - Mar 2008
Externally publishedYes


  • Calcium
  • Contraction
  • G proteins
  • Signal transduction
  • Transgenic mice


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