Rate dependence of isoproterenol-stimulated phosphorylase a formation in mouse heart.
In mouse right ventricular strips, field-stimulated to contract isometrically in an oxygenated bicarbonate-buffered physiological salt solution at 22--24 degrees C, isoproterenol (3 microM) stimulation of phosphorylase a accumulation was approximately a linear function of the rate of contraction from 0.2 to 5 Hz. In muscles incubated in the absence of isoproterenol, the phosphorylase a activity did not increase when the contraction frequency was varied over this range. At a low frequency of stimulation (0.2 Hz), phosphorylase a activity was not increased after a 5-min exposure to 3 microM isoproterenol, as compared to a 4-fold increase in phosphorylase a activity at a high frequency (3.-3 Hz). Isoproterenol (3 microM) increased tissue cyclic AMP content and the activated form of phosphorylase kinase activity to similar extents at both frequencies. N6,O2'-dibutyryl cyclic AMP increased the phosphorylase a activity at both frequencies but the increase at 3.3 Hz was approximately 3-fold greater than at 0.2 Hz. Verapamil did not block isoproterenol-stimulated phosphorylase a activity at 3.3 Hz at a concentration (0.6 microM) that inhibited the increased sensitivity to the inotropic action of isoproterenol seen at high frequencies of contraction. Isoproterenol stimulation of phosphorylase a accumulation did not correlate with developed tension. It is proposed that the difference in isoproterenol stimulation of phosphorylation b to a conversion at 0.2 and 3.3 Hz primarily results from a difference in Ca++ control of the activity of the activated form of phosphorylase kinase.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006339:Heart Rate; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000378:metabolism; D010762:Phosphorylase a / Q000096:biosynthesis*; D006005:Phosphorylases / Q000096:biosynthesis*
D000242:Cyclic AMP; D010762:Phosphorylase a; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D007545:Isoproterenol