Effects of low-level α-myosin heavy chain expression on contractile kinetics in porcine myocardium
Open accessAbstract
Myosin heavy chain (MHC) isoforms are principal determinants of work capacity in mammalian ventricular myocardium. The ventricles of large mammals including humans normally express ∼10% α-MHC on a predominantly β-MHC background, while in failing human ventricles α-MHC is virtually eliminated, suggesting that low-level α-MHC expression in normal myocardium can accelerate the kinetics of contraction and augment systolic function. To test this hypothesis in a model similar to human myocardium we determined composite rate constants of cross-bridge attachment ( f app) and detachment ( g app) in porcine myocardium expressing either 100% α-MHC or 100% β-MHC in order to predict the MHC isoform-specific effect on twitch kinetics. Right atrial (∼100% α-MHC) and left ventricular (∼100% β-MHC) tissue was used to measure myosin ATPase activity, isometric force, and the rate constant of force redevelopment ( k tr) in solutions of varying Ca 2+concentration. The rate of ATP utilization and k tr were approximately ninefold higher in atrial compared with ventricular myocardium, while tension cost was approximately eightfold greater in atrial myocardium. From these values, we calculated f app to be ∼10-fold higher in α- compared with β-MHC, while g app was 8-fold higher in α-MHC. Mathematical modeling of an isometric twitch using these rate constants predicts that the expression of 10% α-MHC increases the maximal rate of rise of force (dF/d t max) by 92% compared with 0% α-MHC. These results suggest that low-level expression of α-MHC significantly accelerates myocardial twitch kinetics, thereby enhancing systolic function in large mammalian myocardium.
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Swine ventricles predominantly express beta-MHC (~100%, 87% sub-epicardium, 97% sub-endocardium), similar to humans (>90-95%).
“Swine ventricles predominately express β-MHC (~100%, 87% sub-epicardium, 97% sub-endocardium) similar to humans’ (>90–95%) (Hamilton & Ianuzzo, 1991; Locher, et al., 2011; Miyata, et al., 2000; Reiser, et al., 2001; Stelzer, et al., 2008).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Locher, et al., 2011
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Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
- Authors
- Locher, M. R., Razumova, M. V., Stelzer, J. E., Norman, H. S., & Moss, R. L.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Washington (US)
- Corresponding author
- Locher, Matthew R.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2011-03
- Volume
- 300
- Issue
- 3
- Pages
- H869-H878
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- PMC
- PMC3064314
- OpenAlex
- W1992084236
- Cited by
- 47
- References
- 54
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 2 · 2015: 3 · 2013: 8 · 2012: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL061635, HL-61635)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- myosin heavy chain isoforms, alpha-myosin heavy chain, beta-myosin heavy chain, twitch kinetics, myosin ATPase activity, systolic function, calcium dependence, porcine myocardium
- MeSH terms
- Animals, Calcium, Female, Heart, Male, Myocardial Contraction, Myocardium, Myosins, Swine, Myosin Heavy Chains, Ventricular Myosins, Muscle Strength
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