Journal article
Diversity and similarity of motor function and cross-bridge kinetics in papillary muscles of transgenic mice carrying myosin regulatory light chain mutations D166V and R58Q
Journal of molecular and cellular cardiology, Vol.62, pp.153-163
09/2013
DOI: 10.1016/j.yjmcc.2013.05.012
PMCID: PMC3809071
PMID: 23727233
Abstract
Mechanical properties of skinned papillary muscle fibers from transgenic mice expressing familial hypertrophic cardiomyopathy associated mutations D166V and R58Q in myosin regulatory light chain were investigated. Elementary steps and the apparent rate constants of the cross-bridge cycle were characterized from the tension transients induced by sinusoidal length changes during maximal Ca2+ activation, together with ATP, ADP, and Pi studies. The tension–pCa relation was also tested in two sets of solutions with differing Pi and ionic strength. Our results showed that in both mutants the fast apparent rate constant 2πc and the rate constants of the cross-bridge detachment step (k2) were smaller than those of wild type (WT), demonstrating the slower cross-bridge kinetics. D166V showed significantly smaller ATP (K1) and ADP (K0) association constants than WT, displaying weaker ATP binding and easier ADP release, whereas those of R58Q were not significantly different from WT. In tension–pCa study, both D166V and R58Q mutations exhibited increased Ca2+ sensitivity and less cooperativity. We conclude that, while the two FHC mutations have similar clinical manifestations and prognosis, some of the mechanical parameters of cross-bridges (K0, K1) are differently modified, whereas some others (Ca2+-sensitivity, cooperativity, k2) are similarly modified by these two FHC associated mutations.
•FHC mutations D166V and R58Q of myosin RLC were investigated in Tg mouse models.•Papillary muscles were characterized by sinusoidal analysis with ATP, ADP and Pi study.•Tension, stiffness, and rigor stiffness in mutants did not differ from the wild type.•Both mutants showed slower crossbridge detachment rate and increased Ca2+ sensitivity.•D166V but not R58Q exhibited weaker ATP binding and faster ADP release.
Details
- Title: Subtitle
- Diversity and similarity of motor function and cross-bridge kinetics in papillary muscles of transgenic mice carrying myosin regulatory light chain mutations D166V and R58Q
- Creators
- Li Wang - University of IowaPriya Muthu - University of MiamiDanuta Szczesna-Cordary - University of IowaMasataka Kawai - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.62, pp.153-163
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.yjmcc.2013.05.012
- PMID
- 23727233
- PMCID
- PMC3809071
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: HL070041, HL108343, HL071778, HL090786; DOI: 10.13039/100000968, name: American Heart Association, award: 10POST3420009
- Language
- English
- Date published
- 09/2013
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984284324902771
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