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Cardiovascular Research 2004 61(4):756-763; doi:10.1016/j.cardiores.2003.12.019
© 2004 by European Society of Cardiology
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Copyright © 2004, European Society of Cardiology

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

James R Peñaa and Beata M Wolska*,a,b

aProgram in Cardiovascular Sciences, Department of Medicine, Section of Cardiology, University of Illinois at Chicago, Chicago, IL 60612, USA
bDepartment of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA

* Corresponding author. Department of Medicine, Section of Cardiology (M/C 715), University of Illinois, 840 S. Wood Street, Chicago, IL 60612, USA. Tel.: +1-312-4130240; fax: +1-312-9965062. bwolska{at}uic.edu

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 β-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 TnI (PLB/ssTnI) 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/cTnI and PLB/ssTnI groups. However, hearts expressing ssTnI (PLB/ssTnI) showed a significantly decreased rate of relaxation (–dP/dt) when compared with hearts expressing cTnI (PLB/cTnI). In response to β-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/ssTnI than in PLB/cTnI hearts. In the basal state, there was no difference in HR, DP, LVEDP,+dP/dt and –dP/dt between PLBKO/cTnI 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 β-adrenergic stimulation.

KEYWORDS Troponin I; Phospholamban; β-Adrenergic stimulation; Relaxation


Time for primary review 22 days


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