Differential effects of myosin light chain kinase inhibition on contractility, force development and myosin light chain 20 phosphorylation of rat cervical and thoracic duct lymphatics
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Non‐Technical Summary The contractile activities of lymphatic muscle cells, which are the key for the lymphatic function, vary between lymphatic beds. We show that pressure‐dependent changes and myosin light chain kinase (MLCK) inhibition differentially affect myosin light chain 20 (MLC 20) phosphorylation in lymphatic muscle, thereby controlling the contractile behaviour of thoracic duct and cervical lymphatics. Our findings suggest that pressure‐induced changes in lymphatic contractile function act through MLC 20 di‐phosphorylation to modulate lymphatic tonic contractions, whereas the MLCK inhibitor ML‐7 affects both mono‐ and di‐phosphorylation of MLC 20 and consequently decreases tonic contractions. In addition, our data indicate that ML‐7 affects pacemaking activity of lymphatic muscle, and thereby decreases the lymphatic phasic contraction frequency. Thus the statuses of MLC 20 phosphorylation play essential roles in regulating the contractile activities of lymphatics.
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Spontaneous lymphatic contractions are regulated by the phosphorylation of myosin light chain 20 through the balance of myosin light chain kinase/phosphatase activities.
“Spontaneous lymphatic contractions are regulated by the phosphorylation of myosin light chain 20 through the balance of myosin light chain kinase/phosphatase activities (62, 63).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [62]
The Discussion (Fig. 7; page unavailable) reports that inhibiting myosin light chain kinase reduces MLC20 phosphorylation and tonic contraction, and can reduce phasic contraction frequency. It presents a role for myosin light chain phosphatase as a possible, not directly tested, pathway; it also says the effect on phasic pumping may involve other proteins. The claimed kinase/phosphatase balance as an established regulator of spontaneous contractions therefore goes beyond the findings. (LLM, conf=0.86)
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The specificities of protein kinase inhibitors: an update
BAIN, J., McLAUCHLAN, H., ELLIOTT, M., & COHEN, P. (2003) · Biochemical Journal · doi:10.1042/bj20021535 · Cited by 1,369 · cited 1× · see citing works
“We kept ML-7 concentrations in the range (from 10−7 M to 10−5 M) that had been reported to be specific for MLCK inhibition (Bain et al. 2003; Wang et al. 2009).”
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Research works printed but not linked: 2
- C 2011 The Authors. Journal compilation C 2011 The Physiological Society 14697793, 2011, 22, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.1113/jphysiol.2011.218446 by Mount Vernon Nazarene University, Wiley Online Library on [23/06/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License J Physiol 589. · DOI
- Mislin H (1966). Structural and functional relations of the mesenteric lymph vessels. New Trends in Basic Lymphology; Proceedings of a Symposium held at Charleroi (Belgium); July 11-13, 1966. Experientia 14, 87-96.
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Transport and Immune Functions of the Lymphatic System.
Davis, M. J., Zawieja, S. D., & King, P. D. (2025) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022724-104908 · Cited by 42 · see citing works
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- Authors
- Nepiyushchikh, Z. V., Chakraborty, S., Wang, W., Davis, M. J., Zawieja, D. C., & Muthuchamy, M.
- Affiliations
- Texas A&M Health Science Center (US)
- University of Missouri (US)
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2011-11
- Volume
- 589
- Issue
- 22
- Pages
- 5415-5429
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC3240881
- OpenAlex
- W1531642080
- Cited by
- 37
- References
- 1
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 1 · 2012: 3
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Lymphatic Research Foundation
- National Institutes of Health (KO2 HL86650, HL80526, HL86650)
- National Heart, Lung, and Blood Institute (HL089784, R01HL080526, R01 HL80526, K02HL086650, R01-HL-75199, R01 HL96552, K02 HL86650, R01HL075199, R01HL096552, R01HL089784)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- lymphatic contractility, myosin light chain kinase, ML-7, myosin light chain 20 phosphorylation, tonic contraction, phasic contractions, transmural pressure, isometric force, smooth muscle contraction regulation
- MeSH terms
- Animals, Azepines, Enzyme Inhibitors, Lymphatic System, Male, Muscle Contraction, Myosin-Light-Chain Kinase, Naphthalenes, Neck, Phosphorylation, Thoracic Duct, Rats, Sprague-Dawley, Myosin Light Chains, Lymphatic Vessels, Rats, In Vitro Techniques
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