Troponin I phosphorylation plays an important role in the relaxant effect of β-adrenergic stimulation in mouse hearts

Objective: The present study was designed to address the question of the contribution of cardiac troponin I (cTnI) phosphorylation to the enhanced rate of relaxation during p-adrenergic stimulation in hearts in situ. Methods: In situ hemodynamic measurements were performed in mouse hearts that (1) express normal level of phospholamban (PLB) and either express cTnI (PLB/cTnI) or the slow skeletal isoform of Tril (PLB/ssTnl) that cannot be phosphorylated by protein kinase A (PKA) or (2) do not express PLB and either express cTnI (PLBKO/cTnI) or ssTnI (PLBKO/ssTnI). Results: In the basal state, there was no difference in heart rate (HR), developed pressure (DP), left ventricular end-diastolic pressure (LVEDP) or rate of contraction ( + dP/dt) between PLB/cTnl and PLB/ssTnI groups. However, hearts expressing ssTnI (PLB/ssTnl) showed a significantly decreased rate of relaxation ( - dP/dt) when compared with hearts expressing cTnI (PLB/cTnl). In response to p-adrenergic agonist, isoproterenol (ISO), HR increased similarly in both groups. At the two highest doses of ISO, the rate of relaxation (- dP/dt) was significantly smaller in PLB/ssTnl than in PLB/cTnl hearts. In the basal state, there was no difference in HR, DP, LVEDP, + dP/dt and -dP/dt between PLBKO/cTnl and PLBKO/ssTnI hearts. In response to ISO, HR increased similarly in both groups and was only slightly smaller in PLBKO/ssTnI group at the lowest dose of ISO. However, during ISO perfusion, when cTnI was phosphorylated, the rate of relaxation was significantly slower in PLBKO/ssTnI compared to PLBKO/cTnI hearts. Conclusion: Our data support the hypothesis that phosphorylation of cTnI significantly contributes to the enhanced rate of relaxation during p-adrenergic stimulation. (C) 2004 European Society of Cardiology. Published by Elsevier B.V All rights reserved.