SLOWING OF SHORTENING VELOCITY OF RAT CARDIAC MYOCYTES BY ADENOSINE RECEPTOR STIMULATION REGARDLESS OF BETA-ADRENERGIC STIMULATION

1. Single ventricular myocytes were enzymatically isolated, incubated with the A(1)-purinergic and beta-adrenergic receptor-specific agonist s N-6-cyclopentyladenosine (CPA) and isoprenaline (Iso), and then rapi dly skinned. Ca2+ sensitivity of isometric tension and unloaded shorte ning velocity (V-0)were measured, and protein kinase A (PKA)-specific phosphorylations of troponin I (TnI) and C-protein were assessed by ba ck-phosphorylation of cell suspensions with [gamma-P-32]-ATP. 2. Isopr enaline treatment decreased the Ca2+ sensitivity of isometric tension relative to propranolol-treated controls, as did simultaneous stimulat ion with Iso and CPA (Iso + CPA). CPA alone had no effect on Ca2+ sens itivity. V-o was greater in Iso-treated cells than in paired controls, while V-0 was significantly less than control in both Iso + CPA-treat ed and CPA-treated cells. 3. Phosphorylation of TnI and C-protein was increased by Iso treatment and also when Iso and CPA were simultaneous ly applied. CPA alone caused a significant decrease in the phosphoryla tion state of these two proteins. 4. From these results we conclude th at A(1)-purinergic receptor stimulation does not inhibit beta-adrenerg ic receptor-mediated phosphorylation of myofilament proteins, nor does it alter the Ca2+ sensitivity of isometric tension at the level of th e myofilaments. However, A(1)-receptor stimulation does decrease V-0 a t the level of the myofilaments by a mechanism that is independent of beta-adrenergically mediated phosphorylation of TnI and C-protein.