Contractility of myofibrils from the heart and diaphragm muscles measured with atomic force cantilevers: Effects of heart-specific deletion of arginyl-tRNA-protein transferase

BackgroundContractile properties of myofibrils from the myocardium and diaphragm in chronic heart failure are not well understood. We investigated myofibrils in a knockout (KO) mouse model with cardiac-specific deletion of arginyl-tRNA-protein transferase (α-MHCAte1), which presents dilated cardiomyopathy and heart failure.ObjectiveThe aim of this study was to test the hypothesis that chronic heart failure in α-MHCAte1 mice is associated with abnormal contractile properties of the heart and diaphragm.MethodsWe used a newly developed system of atomic force cantilevers (AFC) to compare myofibrils from α-MHCAte1 and age-matched wild type mice (WT). Myofibrils from the myocardium and the diaphragm were attached to the AFC used for force measurements during activation/deactivation cycles at different sarcomere lengths.ResultsIn the heart, α-MHCAte1 myofibrils presented a reduced force during full activation (89 ± 9 nN/μm2) when compared to WT (132 ± 11 nN/μm2), and the decrease was not influenced by sarcomere length. These myofibrils presented similar kinetics of force development (Kact), redevelopment (Ktr), and relaxation (Krel). In the diaphragm, α-MHCAte1 myofibrils presented an increased force during full activation (209 ± 31 nN/μm2) when compared to WT (123 ± 20 nN/μm2). Diaphragm myofibrils of α-MHCAte1 and WT presented similar Kact, but α-MHCAte1 myofibrils presented a faster Krel (6.11 ± 0.41 s− 1 vs 4.63 ± 0.41 s− 1).ConclusionContrary to our working hypothesis, diaphragm myofibrils from α-MHCAte1 mice produced an increased force compared to myofibrils from WT. These results suggest a potential compensatory mechanism by which the diaphragm works under loading conditions in the α-MHCAte1 chronic heart failure model.