Journal article
Ca2+ activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T
American journal of physiology. Heart and circulatory physiology, Vol.280(2), pp.H705-H713
02/01/2001
Handle:
https://hdl.handle.net/2376/113915
PMID: 11158969
Abstract
The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not well understood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model in which 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca2+ than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca2+ (pCa50) = 5.84 ± 0.01 and 6.12 ± 0.01 for NTG and TG fibers, respectively]. The shift in pCa50 caused by increasing the sarcomere length from 1.9 to 2.3 μm was significantly higher for TG than for NTG fibers (ΔpCa50 = 0.13 ± 0.01 and 0.29 ± 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady-state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca2+ in TG than in NTG fibers (pCa50 = 5.71 ± 0.02 and 6.07 ± 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca2+ sensitivity in TG myofilaments.
Metrics
9 Record Views
Details
- Title
- Ca2+ activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T
- Creators
- Murali Chandra - Department of Physiology and Biophysics and Cardiovascular Sciences Program, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612Veronica L. M Rundell - Department of Physiology and Biophysics and Cardiovascular Sciences Program, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612Jil C Tardiff - Department of Medicine, Albert Einstein College of Medicine, The Bronx, New York 10461; andLeslie A Leinwand - Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309Pieter P de Tombe - Department of Physiology and Biophysics and Cardiovascular Sciences Program, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612R. John Solaro - Department of Physiology and Biophysics and Cardiovascular Sciences Program, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.280(2), pp.H705-H713
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Identifiers
- 99900548242401842
- Language
- English
- Resource Type
- Journal article