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

Background: Contractile properties ofmyofibrils from themyocardium and diaphragm in chronic heart failure are notwell understood. Weinvestigated myofibrils in a knockout (KO) mouse modelwith cardiac-specific deletionof arginyl-tRNA-protein transferase (alpha-MHCAte1), which presents dilated cardiomyopathy and heart failure. Objective: The aim of this study was to test the hypothesis that chronic heart failure in alpha-MHCAte1 mice is associated with abnormal contractile properties of the heart and diaphragm. Methods: We used a newly developed system of atomic force cantilevers (AFC) to compare myofibrils from alpha-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. Results: In the heart, alpha-MHCAte1 myofibrils presented a reduced force during full activation (89 +/- 9 nN/mu m(2)) when compared to WT (132 +/- 11 nN/mu m(2)), 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, alpha-MHCAte1 myofibrils presented an increased force during full activation (209 +/- 31 nN/mu m(2)) when compared to WT (123 +/- 20 nN/mu m(2)). Diaphragm myofibrils of alpha-MHCAte1 and WT presented similar Kact, but alpha-MHCAte1 myofibrils presented a faster Krel (6.11 +/- 0.41 s(-1) vs 4.63 +/- 0.41 s(-1)). Conclusion: Contrary to our working hypothesis, diaphragm myofibrils from alpha-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 alpha-MHCAte1 chronic heart failure model. (C) 2013 Elsevier Ireland Ltd. All rights reserved.