title: Contractility of myofibrils from the heart and diaphragm muscles measured with atomic force cantilevers: effects of heart-specific deletion of arginyl-tRNA-protein transferase.
abstract: BACKGROUND
  Contractile 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In the heart, α-MHCAte1 myofibrils presented a reduced force during full activation (89±9 nN/μm(2)) when compared to WT (132±11 nN/μm(2)), and the decrease was not influenced by sarcomere length. These myofibrils presented similar kinetics of force development (K(act)), redevelopment (K(tr)), and relaxation (K(rel)). In the diaphragm, α-MHCAte1 myofibrils presented an increased force during full activation (209±31 nN/μm(2)) when compared to WT (123±20 nN/μm(2)). Diaphragm myofibrils of α-MHCAte1 and WT presented similar K(act), but α-MHCAte1 myofibrils presented a faster K(rel) (6.11±0.41s(-1) vs 4.63±0.41 s(-1)).
  
  
  CONCLUSIONS
  Contrary 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.
authors.affiliation: Exercise Pathophysiology Research Laboratory and Cardiology Division, Hospital de Clínicas de Porto Alegre, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Paula A B
authors.initials: PA
authors.lastname: Ribeiro
authors.forename: Jorge P
authors.initials: JP
authors.lastname: Ribeiro
authors.forename: Fábio C
authors.initials: FC
authors.lastname: Minozzo
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavlov
authors.forename: Nicolae A
authors.initials: NA
authors.lastname: Leu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kurosaka
authors.forename: Anna
authors.initials: A
authors.lastname: Kashina
authors.forename: Dilson E
authors.initials: DE
authors.lastname: Rassier
mesh_terms: D019881:Aminoacyltransferases / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001696:Biomechanical Phenomena / Q000235:genetics; D003964:Diaphragm / Q000502:physiology*; D004195:Disease Models, Animal; D017353:Gene Deletion; D006321:Heart / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics*; D009200:Myocardial Contraction / Q000235:genetics; D009206:Myocardium / Q000201:enzymology; D009210:Myofibrils / Q000235:genetics*
chemical_list: D019881:Aminoacyltransferases; C019727:arginyltransferase
keywords: Arginylation; Atomic force cantilever; Cardiomyopathy; Myofibrils