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)).

CONCLUSION:

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: Paula A B Ribeiro, Jorge P Ribeiro, Fábio C Minozzo, Ivan Pavlov, Nicolae A Leu, Satoshi Kurosaka, Anna Kashina, Dilson E Rassier
• Journal: International journal of cardiology (Int J Cardiol) Vol. 168 Issue 4 Pg. 3564-71 (Oct 09 2013) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 23739549 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Aminoacyltransferases
• arginyltransferase

Topics

• Aminoacyltransferases (deficiency, genetics)
• Animals
• Biomechanical Phenomena (genetics)
• Diaphragm (physiology)
• Disease Models, Animal
• Gene Deletion
• Heart (physiology)
• Mice
• Mice, Knockout
• Muscle Contraction (genetics)
• Myocardial Contraction (genetics)
• Myocardium (enzymology)
• Myofibrils (genetics)