Effects of adenosine and protein kinase C stimulation on mechanical properties of rat cardiac myocytes.
Exposure of the heart to adenosine decreases heart rate and left ventricular developed pressure. However, little is known regarding the influence of adenosine on mechanical properties of isolated ventricular myocytes and the intracellular mechanism(s) by which adenosine acts. Therefore, in the present study we compared the effects of the adenosine receptor agonist R-phenylisopropyladenosine (R-PIA) and protein kinase C (PKC) activator dioctanoylglycerol (DOG) on Ca2+ sensitivity of tension, maximum isometric tension, and velocity of unloaded shortening (Vmax) in enzymatically isolated, drug-treated, and subsequently skinned ventricular myocytes. Neither R-PIA (100 microM) nor DOG (50 microM) affected Ca2+ sensitivity of tension or maximum isometric tension compared with controls. However, both R-PIA and DOG treatment caused approximately 25% decrease in Vmax during maximum activation compared with controls. This suggests adenosine and PKC decrease actin-myosin interaction through an alteration of myofilament proteins. The observed similarity of response after R-PIA and DOG treatment is consistent with the hypothesis that effects of adenosine are mediated by activation of the PKC pathway in isolated ventricular myocytes.
Lester
J W
JW
Department of Physiology and Biophysics, College of Medicine, University of Tennessee, Memphis 38163, USA.
Gannaway
K F
KF
Reardon
R A
RA
Koon
L D
LD
Hofmann
P A
PA
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D010660:Phenylisopropyladenosine; D011493:Protein Kinase C; D000241:Adenosine; D007545:Isoproterenol