The G-Protein G₀ in Mammalian Cardiac Muscle: Localization and Coupling to A₁ Adenosine Receptors

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To investigate the functional relevance of the G-protein G₀ to adenosine-induced effects in the heart, we studied the localization of G₀ and its interaction with A₁ adenosine receptors. Concentrations of G₀ in various mammalian hearts differed markedly between the atrial and the ventricular muscle, as well as among species. In most species examined, the concentration of G₀ was much higher in the atrium than in the ventricle. The highest levels of G₀ in atria and ventricles were found in the ferret heart. An immunohistochemical study of the ferret heart with G₀α-specific antibodies showed that G₀ was localized throughout the membranes of cardiac myocytes, including the intercalated disks. In addition, G₀ was densely distributed in the nerve fibers and Purkinje fibers. Analyses of G₀α subtypes showed that bovine atrium mainly contained G₀Aα, while bovine ventricle contained only G₀Bα. By contrast, ferret ventricle contained both subtypes of G₀α. To study the coupling of G₀ to A₁ adenosine receptors, receptors in ventricular membranes of ferrets, which had been pretreated with pertussis toxin, or purified receptors were reconstituted with purified G₀A and G₀B. The reconstitution experiments indicated that both subtypes of G₀ coupled with A₁ adenosine receptors. These results suggest that the effect of adenosine is mediated by both G₀A and G₀B in membranes of ferret cardiac myocytes.