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

作者:Nepiyushchikh Zhanna V; Chakraborty Sanjukta; Wang Wei; Davis Michael J; Zawieja David C; Muthuchamy Mariappan*
来源:The Journal of Physiology, 2011, 589(22): 5415-5429.
DOI:10.1113/jphysiol.2011.218446

摘要

The intrinsic contractile activity of lymphatics varies in different regions of the body. We have previously shown that cervical lymphatics possess an inherently higher frequency but lower tone at a given pressure when compared to thoracic duct lymphatics. However, the molecular mechanisms modulating the contractile characteristics of these lymphatics are not well understood. Since myosin light chain 20 (MLC(20)) phosphorylation appears to underlie the tonic component of lymphatic contraction, we hypothesized that the thoracic duct would be more sensitive to the modulation of MLC(20) phosphorylation when compared to cervical lymphatics. To test our hypothesis, the contractile activities and MLC(20) phosphorylation of thoracic duct and cervical lymphatics were determined in the absence or presence of the specific myosin light chain kinase (MLCK) inhibitor ML-7 under both isobaric and isometric conditions. Addition of ML-7 at each concentration tested led to a decrease in tone in both vessel types. While ML-7 (10(-6) M) significantly reduced the phasic contraction frequency of cervical lymphatics, it completely stopped phasic contractions of thoracic duct at that concentration. Under isometric conditions the active peak and plateau components of tension were both significantly higher in thoracic duct compared to cervical lymphatics. ML-7 (10(-5) M) significantly decreased both the active peak and plateau tensions of thoracic duct, whereas only the active peak tension of cervical lymphatics was decreased. In thoracic duct MLC(20) di-phosphorylation, but not mono-phosphorylation, was significantly decreased with increasing transmural pressure, whereas in cervical vessels only at the higher pressures tested did MLC(20) di-phosphorylation decrease. ML-7 treatment of the thoracic duct caused a significant decrease in both the mono-and di-phosphorylated forms of MLC(20).

  • 出版日期2011-11