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The in vitro motility activity of β-cardiac myosin depends on the nature of the β-myosin heavy chain gene mutation in hypertrophic cardiomyopathy
Abstract
Several mutations in the beta-myosin heavy chain gene cause hypertrophic cardiomyopathy. This study investigates (1) the in vitro velocities of translocation of fluorescently-labelled actin by beta-myosin purified from soleus muscle of 30 hypertrophic cardiomyopathy patients with seven distinct beta-myosin heavy chain gene mutations: Thr124Ile, Tyr162Cys, Gly256Glu, Arg403Gln, Val606Met, Arg870His, and Leu908Val mutations; and (2) motility activity of beta-myosin purified from cardiac and soleus muscle biopsies in the same patients. The velocity of translocation of actin by beta-myosin purified from soleus or cardiac muscle of 22 normal controls was 0.48 +/- 0.09 micron s-1. By comparison, the motility activity was reduced in all 30 patients with beta-myosin heavy chain gene mutations (range, 0.112 +/- 0.041 to 0.292 +/- 0.066 micron s-1. Notably, the Tyr162Cys and Arg403Gln mutations demonstrated significantly lower actin sliding velocities: 0.123 +/- 0.044, and 0.112 +/- 0.041 micron s-1, respectively. beta-myosin purified from soleus muscle from four patients with the Arg403Gln mutation had a similar actomyosin motility activity compared to beta-myosin purified from their cardiac biopsies (0.127 +/- 0.045 micron s-1 versus 0.119 +/- 0.068 micron s-1, respectively). Since these seven mutations lie in several distinct functional domains, it is likely that the mechanisms of their inhibitions of motility are different.
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“Such an increased energetic cost of contraction with the Arg403Gln mutation in the intact mouse heart3 is thought to be consistent with several molecular studies suggesting a decrease in actomyosin motility20,21 that effectively puts an energetic “drag” on the wild-type myosin during shortening3,19,22.”
From iRhythm ZIO: The Diagnostic Yield of a 14-day Continuous Ambulatory ECG Monitor (Turakhia et al., diagnostic yield of extended ambulatory ECG monitoring) (2013) · cites this paper as [20]
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Research works printed but not linked: 1
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Metadata
- Authors
- CUDA, G., FANANAPAZIR, L., EPSTEIN, N. D., & SELLERS, J. R.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Muscle Research & Cell Motility
- Published
- 1997-05
- Volume
- 18
- Issue
- 3
- Pages
- 275-283
- ISSN
- 0142-4319 (ISSN-L)
- 1573-2657
- OpenAlex
- W383489959
- Cited by
- 137
- References
- 39
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 2
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Muscle Research and Cell Motility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- hypertrophic cardiomyopathy, beta-myosin heavy chain, myosin mutations, actomyosin motility, soleus muscle, myocardium, cardiac contractility
- MeSH terms
- Actins, Cardiomyopathy, Hypertrophic, Humans, Models, Biological, Myocardium, Myosins, Muscle, Skeletal, Myosin Heavy Chains
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