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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. |
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| Name(s): |
Wen, Yuhui, author Xu, Yuanyuan, author Wang, Yingcai, author Pinto, Jose, author Potter, James, author Kerrick, W., author |
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| Type of Resource: | text | |
| Genre: | Text | |
| Issuance: | serial | |
| Date Issued: | 2009 | |
| Physical Form: |
computer online resource |
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| 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'>http://www.sciencedirect.com/science/article/pii/S002228360900970X">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 Therapeutics Cardiovascular system -- Diseases Cells Chemicals Drugs Cardiovascular system Physiology Respiratory organs Genetics Heterocyclic compounds Investigations Medical sciences Eye Musculoskeletal system Neurophysiology Nucleic acids Nucleosides Tissues |
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| Links: | http://dx.doi.org/10.1016/j.jmb.2009.07.080 | |
| Persistent Link to This Record: | http://purl.flvc.org/fsu/fd/FSU_migr_biomed_faculty_publications-0060 | |
| Owner Institution: | FSU | |
| Is Part of Series: | Department of Biomedical Sciences Faculty Publications. | |
| Is Part Of: | Journal of Molecular Biology. | |
| Issue: | 5, 392 |
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 http://dx.doi.org/10.1016/j.jmb.2009.07.080
