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We hypothesized that the extent of frequency-dependent acceleration of relaxation (FDAR) would be less than that of isoproterenol-(ISO-)dependent acceleration of relaxation (IDAR) at the same increment of heart rates, and ISO may improve FDAR. Cardiac function and phosphorylation of PLB and cTnI were compared in pacing, ISO treatment, and combined pacing and ISO treatment in isolated working heart. The increase in cardiac output and the degree of relaxation was less in pacing than in ISO treatment at the same increment of heart rates. The increasing stimulation frequency induced more significant relaxant effect in ISO perfusion than that in physiological salt perfusion. The pacing only phosphorylated PLB at Thr17, but ISO induced phosphorylation of cTnI and PLB at Ser16 and Thr17. Those results suggest that the synergistic effects of PLB and cTnI induce higher degree of relaxation which makes a sufficient diastolic filling of the ventricle at higher heart rate.

Synergistic Effects between Phosphorylation of Phospholamban and Troponin I Promote Relaxation at Higher Heart Rate