Phospholamban modulates murine atrial contractile parameters and responses to beta-adrenergic agonists.
Phospholamban gene transcript levels are much lower in murine atria as compared to murine ventricles and this reduced phospholamban expression has been suggested to result in enhanced atrial contractile parameters. To delineate the functional role of phospholamban in murine atrium, the contractile parameters of isolated muscles from phospholamban knockout and cardiac-specific phospholamban overexpression mice along with their isogenic wild-type controls were evaluated. Assessment of the times (ms) to peak tension development and to half-relaxation of developed tension, as well as the rates (mg/s) of tension development and relaxation in paced atrial muscles, revealed that phospholamban ablation was associated with enhanced rates of relaxation with no significant effect on contraction rate, while phospholamban overexpression (three-fold) was associated with depressed rates of both contraction and relaxation. Isoproterenol stimulation resulted in significant increases in the rates of developed tension and relaxation in both phospholamban deficient and phospholamban overexpression atria, indicating that the beta-adrenergic pathway was functional in these muscles. These findings suggest that phospholamban is an important modulator of atrial contractility and its responses to beta-adrenergic agonists.
Kadambi
V J
VJ
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575, USA.
Koss
K L
KL
Grupp
I L
IL
Kranias
E G
EG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D000099211:Phospholamban
D000318:Adrenergic beta-Agonists; D002135:Calcium-Binding Proteins; D007545:Isoproterenol; D000099211:Phospholamban