Enhanced calcium cycling and contractile function in transgenic hearts expressing constitutively active G alpha o* protein

American Journal of Physiology. Heart and Circulatory Physiology
Ming ZhuUlrike Mende

Abstract

In contrast to the other heterotrimeric GTP-binding proteins (G proteins) Gs and Gi, the functional role of G o is still poorly defined. To investigate the role of G alpha o in the heart, we generated transgenic mice with cardiac-specific expression of a constitutively active form of G alpha o1* (G alpha o*), the predominant G alpha o isoform in the heart. G alpha o 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 G alpha o* transgenic mice in vivo, along with increased L-type Ca2+ channel current density, calcium transients, and cell shortening in ventricular G alpha o*-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 G alpha o* ventricles. Density and affinity of beta-adrenoceptors, cAMP ...Continue Reading

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Citations

Feb 18, 2011·Cell Biochemistry and Biophysics·Ilka PinzJoanne S Ingwall
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Oct 4, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Zia ZuberiAndrew Tinker
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Feb 7, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Toshihide KashiharaMitsuhiko Yamada

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