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1 Physiology & Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States
2 Chicago, Illinois, United States; Physiology & Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States
3 Cardiology, University of Illinois at Chicago, Chicago, Illinois, United States
4 Physiology & Biophysics, University of Illinois at Chicago, Chicago, Illinois, United States; Cardiology, University of Illinois at Chicago, Chicago, Illinois, United States
* To whom correspondence should be addressed. E-mail: pdetombe{at}uic.edu.
Whether left ventricular (LV) myofilament function is depressed in experimental left ventricular hypertrophy (LVH) or congestive heart failure (CHF) is at present unclear. To address this issue, we studied pressure overload induced left ventricular hypertrophy (POLVH) and myocardial infarction elicited congestive heart failure (MICHF) in rats. LV myocytes were isolated from control, POLVH, and MICHF hearts by mechanical homogenization, Triton-skinned, and attached to micro-pipettes that projected from a sensitive force transducer and high-speed motor. A subset of cells was treated with either unphosphorylated, recombinant cardiac troponin (cTn) or cTn purified from either control or failing ventricles. LV myofilament function was characterized by the force-[Ca2+] relation yielding Ca2+-saturated maximal force (Fmax), myofilament Ca2+-sensitivity (EC50), and cooperativity (nHill) parameters. POLVH was associated with a 35% reduction in Fmax and 36% increase in EC50. Similarly, MICHF resulted in a 42% reduction in Fmax and a 30% increase in EC50. Incorporation of recombinant cTn or purified control cTn into failing cells restored myofilament Ca2+-sensitivity toward levels observed in control cells. In contrast, integration of cTn purified from failing ventricles into control myocytes increased EC50 to levels observed in failing myocytes. The Fmax parameter was not markedly affected by troponin exchange. cTnI phosphorylation was increased in both POLVH and MICHF left ventricles. We conclude that depressed myofilament Ca2+-sensitivity in experimental LVH and CHF is due, in part, to a decreased functional role of cTn that likely involves augmented phosphorylation of cTnI.
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