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Regulation of lymphatic contractility by myosin light chain phosphorylation
Author(s) -
Nepiyushchikh Zhanna V,
Zawieja David C,
Gashev Anatoliy A,
Wang Wei,
Muthuchamy Mariappan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a485-b
Subject(s) - myosin light chain kinase , thoracic duct , lymphatic system , myograph , phosphorylation , myosin , contractility , anatomy , chemistry , biology , microbiology and biotechnology , medicine , endocrinology , pathology , endothelium
One of the basic molecular mechanisms regulating vascular contractility is the phosphorylation of myosin light chain regulatory subunit (MLC20) by myosin light chain kinase (MLCK). To understand the role of myosin light chain phosphorylation in the regulation of lymphatic contractions, we used ML‐7 (10 −6 , 10 −5 M), a specific inhibitor of MLCK in isolated segments of rat thoracic duct and neck lymphatics. The relationships between the circumferential length and tension were measured in thoracic duct and neck lymphatics under basal and activated states (KCl ‐ 140 mM & Substance P ‐ 10 −6 M) using a wire myograph. ML‐7 (10 −6 M) had no significant effect on the tension in either thoracic duct or neck lymphatics. However, the addition of ML‐7 (10 −5 M) tended to decrease active peak (24.21±4.62%, 37.26±5.29%) and plateau (43.37±6.11%, 52.75±6.11%) components of the tensions of neck and thoracic duct lymphatics, respectively. We also determined the relative levels of phosphorylation of MLC20 at different lengths and activation states using Western blot analysis in equivalent isobaric experiments. Inhibition of the signaling pathways, which lead to MLC20 phosphorylation, decreased the development of lymphatic tonic contractile force, potentially leading to increased outflow facility (Funding support NIH ‐ 80526; Postdoctoral Fellowship from Lymphatic Research Foundation).