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Functional Effects of a Restrictive-Cardiomyopathy-Linked Cardiac Troponin I Mutation (R145W) in Transgenic Mice

Title: Functional Effects of a Restrictive-Cardiomyopathy-Linked Cardiac Troponin I Mutation (R145W) in Transgenic Mice.
Name(s): Wen, Yuhui, author
Xu, Yuanyuan, author
Wang, Yingcai, author
Pinto, Jose, author
Potter, James, author
Kerrick, W., author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2009
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The human cardiac troponin I (hcTnI) mutation R145W has been associated with restrictive cardiomyopathy. In this study, simultaneous measurements of ATPase activity and force in skinned papillary fibers from hcTnI R145W transgenic mice (Tg-R145W) were explored. Tg-R145W fibers showed an approximately 13-16% increase in maximal Ca(2+)-activated force and ATPase activity compared to hcTnI wild-type transgenic mice. The force-generating cross-bridge turnover rate (g) and the energy cost (ATPase/force) were the same in all groups of fibers. Also, the Tg-R145W fibers showed a large increase in the Ca(2+) sensitivity of both force development and ATPase. In intact fibers, the mutation caused prolonged force and intracellular [Ca(2+)] transients and increased time to peak force. Analysis of force and Ca(2+) transients showed that there was a 40% increase in peak force in Tg-R145W muscles, which was likely due to the increased Ca(2+) transient duration. The above cited results suggest that: (1) there would be an increase in resistance to ventricular filling during diastole resulting from the prolonged force and Ca(2+) transients that would result in a decrease in ventricular filling (diastolic dysfunction); and (2) there would be a large (approximately 53%) increase in force during systole, which may help to partly compensate for diastolic dysfunction. These functional results help to explain the mechanisms by which these mutations give rise to a restrictive phenotype.
Identifier: FSU_migr_biomed_faculty_publications-0060 (IID), 10.1016/j.jmb.2009.07.080 (DOI)
Keywords: Adenosine Triphosphate, amino acid substitution, cardiomyopathy, restrictive, transgenic, mutation, missense, myocardial contraction, myofibrils, Troponin I
Uncontrolled subjects: Adenosine Triphosphate, Amino Acid Substitution, Animals, Cardiomyopathy, Restrictive, Humans, Mice, Mice, Transgenic, Mutation, Missense, Myocardial Contraction, Myofibrils, Troponin I
Note: Originally published in Journal'>">Journal of Molecular Biology.
Citation: Wen Y1, Xu Y, Wang Y, Pinto JR, Potter JD, & Kerrick WG. (2009). Functional effects of a restrictive-cardiomyopathy-linked cardiac troponin I mutation (R145W) in transgenic mice. J Mol Biol, 392(5):1158-67. doi: 10.1016/j.jmb.2009.07.080.
Subject(s): Diagnosis, Laboratory -- Equipment and supplies
Cardiovascular system -- Diseases
Cardiovascular system
Respiratory organs
Heterocyclic compounds
Medical sciences
Musculoskeletal system
Nucleic acids
Persistent Link to This Record:
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Journal of Molecular Biology.
Issue: 5, 392

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Wen, Y., Xu, Y., Wang, Y., Pinto, J., Potter, J., & Kerrick, W. (2009). Functional Effects of a Restrictive-Cardiomyopathy-Linked Cardiac Troponin I Mutation (R145W) in Transgenic Mice. Journal Of Molecular Biology. Retrieved from