G alpha(q)-coupled receptors in human atrium function through protein kinase C epsilon and delta.
Cardiac G alpha(q)-coupled receptors (such as endothelin, angiotensin, and alpha1-adrenergic receptors) mediate cardiac inotropy and chronotropy, as well as the development of hypertrophy. These receptors signal through protein kinase C (PKC), a family of 12 isozymes including PKC alpha, beta I, beta II, gamma, delta, epsilon, theta, eta, lambda, iota, zeta, and mu. Of these PKC isozymes, alpha, beta II, gamma, epsilon, delta, and zeta have been implicated in signaling through cardiac G alpha(q)-coupled receptors in various animal models. However, the profile of which isozymes are activated by a given G alpha(q)-coupled receptor varies among animal species. Thus, these results can not be extrapolated to human heart. In this study, we examine PKC isozymes activated by three different G alpha(q)-coupled receptors in human atrial tissue. Live atrial appendages obtained from the operating room were sliced and treated with agonists of G alpha(q)-coupled receptors, and cellular redistribution of PKC isozymes was examined by immunoblotting. We find that stimulation of G alpha(q)-coupled receptors in human atrium activates PKC epsilon and delta only, under both acute (5 min) and longer (35 min) stimulations. Further, PKC epsilon and delta exhibit distinct subcellular redistribution patterns; while both translocate to the plasma membrane upon G alpha(q) stimulation, PKC delta also redistributes to mitochondria. We conclude that PKC epsilon and delta are the main PKC isozymes involved in G alpha(q)-mediated signaling in human atria.
Kilts
Jason D
JD
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Grocott
Hilary P
HP
Kwatra
Madan M
MM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016275:Atrial Function; D002478:Cells, Cultured; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006325:Heart Atria / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism
D007527:Isoenzymes; D043562:Receptors, G-Protein-Coupled; D019210:Troponin I; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D043802:GTP-Binding Protein alpha Subunits, Gq-G11