Age increases expression and receptor-mediated activation of G alpha i in human atria.
Recently, we demonstrated that beta2AR and several other Galphas-coupled receptors in human atria also couple to Galphai, a G protein that inhibits adenylyl cyclase (AC). The present study was undertaken to determine whether age increases expression of Galphai in human atrium, and more specifically whether it results in an increase in receptor-mediated activation of Galphai. 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 Galphai2 than atria from mature adults (P < 0.002); this increase in Galphai 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 Galphai 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 Galphai with pertussis toxin, indicating that the age-dependent increases in Galphai expression and activation have functional consequences. Because beta2ARs in human atria mediate contractility through cAMP-mediated phosphorylation of phospholamban, we conclude that an age-induced increase in Galphai may have a role in depressing cardiac function in aged human atria.
Kilts
Jason D
JD
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Akazawa
Toshimasa
T
El-Moalem
Habib E
HE
Mathew
Joseph P
JP
Newman
Mark F
MF
Kwatra
Madan M
MM
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis* / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D018709:Statistics, Nonparametric
D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go