Age Increases Expression and Receptor-Mediated Activation of Gα _i in Human Atria

Recently, we demonstrated that β₂AR and several other Gα_s-coupled receptors in human atria also couple to Gα_i, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Gα_i in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Gα_i. Right atrial appendages were obtained from 14 mature adult (40-55 years) and 14 elderly (71-79 years) patients undergoing cardiac surgery. Immunoblotting of atrial membranes indicates that elderly atria have 82 ± 18% more Gα_i2 than atria from mature adults (P < 0.002); this increase in Gα_i with age is confirmed by pertussis toxin-catalyzed ADP-ribosylation as well as by photoaffinity labeling with [³²P]azidoanilido-GTP. We also find that receptor-mediated activation of Gα_i, is greater in elderly atria and that both basal and receptor-mediated AC activities decrease in elderly atria. These decreases in AC activity can be reversed by disabling Gα_i with pertussis toxin, indicating that the age-dependent increases in Gα _i expression and activation have functional consequences. Because β₂ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Gα_i may have a role in depressing cardiac function in aged human atria.