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

To investigate the functional relevance of the G-protein Go to adenosine-induced effects in the heart, we studied the localization of Go and its interaction with A1 adenosine receptors. Concentrations of Go 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 Go was much higher in the atrium than in the ventricle. The highest levels of Go in atria and ventricles were found in the ferret heart. An immunohistochemical study of the ferret heart with Goa-specific antibodies showed that Go was localized throughout the membranes of cardiac myocytes, including the intercalated disks. In addition, Go was densely distributed in the nerve fibers and Purkinje fibers. Analyses of Goα subtypes showed that bovine atrium mainly contained GoAα, while bovine ventricle contained only GoBα. By contrast, ferret ventricle contained both subtypes of Goα. To study the coupling of Go to A1 adenosine receptors, receptors in ventricular membranes of ferrets, which had been pretreated with pertussis toxin, or purified receptors were reconstituted with purified GoA and GoB. The reconstitution experiments indicated that both subtypes of Go coupled with A1 adenosine receptors. These results suggest that the effect of adenosine is mediated by both GoA and GoB in membranes of ferret cardiac myocytes.