Protein kinase C and the antiadrenergic action of adenosine in rat ventricular myocytes

Miyazaki, Koji, Satoshi Komatsu, Mitsuo Ikebe, Richard A. Fenton, and James G. Dobson, Jr. Protein kinase C and the antiadrenergic action of adenosine in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 287: H1721–H1729, 2004. First published June 17, 2004; 10.1152/ajpheart.00224.2004.—Adenosine-induced antiadrenergic effects in the heart are mediated by adenosine A1 receptors (A1R). The role of PKC in the antiadrenergic action of adenosine was explored with adult rat ventricular myocytes in which PKC was overexpressed. Myocytes were transfected with a pEGFP-N1 vector in the presence or absence of a PKC construct and compared with normal myocytes. The extent of myocyte shortening elicited by electrical stimulation of quiescent normal and transfected myocytes was recorded with video imaging. PKC was found localized primarily in transverse tubules. The A1R agonist chlorocyclopentyladenosine (CCPA) at 1 M rendered an enhanced localization of PKC in the t-tubular system. The -adrenergic agonist isoproterenol (Iso; 0.4 M) elicited a 29–36% increase in myocyte shortening in all three groups. Although CCPA significantly reduced the Isoproduced increase in shortening in all three groups, the reduction caused by CCPA was greatest with PKC overexpression. The CCPA reduction of the Iso-elicited shortening was eliminated in the presence of a PKC inhibitory peptide. These results suggest that the translocation of PKC to the t-tubular system plays an important role in A1R-mediated antiadrenergic actions in the heart.