Experimental LV hypertrophy and congestive heart failure in rats are associated with depressed myofilament Ca2+ sensitivity, partly due to augmented phosphorylation of cTnI.
Does troponin exchange alter myofilament Ca2+ sensitivity in rat models of LV hypertrophy and congestive heart failure?
Depressed myofilament Ca2+ sensitivity in experimental LVH and CHF is partly due to a decreased functional role of cTn, likely involving augmented phosphorylation of cTnI.
It is currently unclear whether left ventricular (LV) myofilament function is depressed in experimental LV hypertrophy (LVH) or congestive heart failure (CHF). To address this issue, we studied pressure overload-induced LV 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, skinned with Triton, and attached to micropipettes 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-Ca 2+ relation yielding Ca 2+ -saturated maximal force (F max ), myofilament Ca 2+ sensitivity (EC 50 ), and cooperativity (Hill coefficient, n H ) parameters. POLVH was associated with a 35% reduction in F max and 36% increase in EC 50 . Similarly, MICHF resulted in a 42% reduction in F max and a 30% increase in EC 50 . Incorporation of recombinant cTn or purified control cTn into failing cells restored myofilament Ca 2+ sensitivity toward levels observed in control cells. In contrast, integration of cTn purified from failing ventricles into control myocytes increased EC 50 to levels observed in failing myocytes. The F max parameter was not markedly affected by troponin exchange. cTnI phosphorylation was increased in both POLVH and MICHF left ventricles. We conclude that depressed myofilament Ca 2+ sensitivity in experimental LVH and CHF is due, in part, to a decreased functional role of cTn that likely involves augmented phosphorylation of cTnI.
Belin et al. (Sat,) conducted a other in Left ventricular hypertrophy and congestive heart failure. Recombinant cardiac troponin (cTn) or purified cTn exchange vs. Control myocytes or untreated failing myocytes was evaluated on Myofilament function characterized by force-[Ca2+] relation (Fmax, EC50, nH). Experimental LV hypertrophy and congestive heart failure in rats are associated with depressed myofilament Ca2+ sensitivity, partly due to augmented phosphorylation of cTnI.