Abstract
In the myocardium the inhibitory guanine nucleotide-binding regulatory proteins (Gi proteins) mediate negative chronotropic and negative inotropic effects by activation of K+ channels and inhibition of adenylyl cyclase. The concept of a uniform inhibitory action of Gi proteins on myocardial cellular activity has been questioned by the recent observations of adenosine-induced activation of the Na+/Ca2+ exchange and a carbachol-induced inhibition of the Na+/K+-ATPase activity in cardiac sarcolemmal membranes. The aim of the present study, therefore, was to reinvestigate the putative regulation of Na+/Ca2+ exchange and Na+/K+-ATPase activity in purified canine sarcolemmal membranes. These membranes were enriched in adenosine A1 (Maximum number of receptors, B max 0.033 pmol/mg) and muscarinic M2 (B max 2.9 pmol/mg) receptors and contained Gi2 and Gi3, two Gi protein isoforms, and Go, another pertussis toxin-sensitive G protein, as detected with specific antibodies. The adenosine A1-selective agonist, (−)-N 6-(2-phenylisopropyl)-adenosine, and the muscarinic agonist, carbachol, both inhibited isoprenaline-stimulated adenylyl cyclase activity by 25% and 35% respectively, and the stable GTP analogue 5′-guanylylimidodiphosphate inhibited forskolin-stimulated adenylyl cyclase activity by 35% in these membranes. The characteristics of Na+/Ca2+ exchange and Na+/K+-ATPase activity as well as those of the ouabain-sensitive, K+-activated 4-nitrophenylphosphatase, an ATP-independent, partial reaction of the Na+/K+-ATPase, were in agreement with published data with regard to specific activity, time course of activity and substrate dependency. However, none of these activities were influenced by adenosine, (−)-N 6-(2-phenylisopropyl)-adenosine, carbachol, or stable GTP analogs, suggesting that Na+/Ca2+ exchange and Na+/K+-ATPase are not regulated by Gi proteins in canine cardiac sarcolemmal membranes.
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Mura, R.A., Zeifang, F., Piacentini, L. et al. Evidence against a regulation of Na+/K+-ATPase by Gi proteins. Failure to detect an influence of G proteins on Na+/Ca2+-exchange in cardiac sarcolemmal membranes. Naunyn-Schmiedeberg's Arch Pharmacol 353, 505–512 (1996). https://doi.org/10.1007/BF00169169
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DOI: https://doi.org/10.1007/BF00169169