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Related Experiment Videos

Calcium and electrical dynamics in lymphatic endothelium.

Erik J Behringer1,2, Joshua P Scallan2,3, Mohammad Jafarnejad4

  • 1Basic Sciences, Loma Linda University, Loma Linda, CA, 92350, USA.

The Journal of Physiology
|October 11, 2017
PubMed
Summary

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Lymphatic endothelial cells (LECs) depolarize, unlike arterial endothelium, due to a lack of specific K+ channels. This electrical signaling facilitates rapid lymph propulsion by promoting coordinated contractions.

Area of Science:

  • Physiology
  • Vascular Biology
  • Cell Signaling

Background:

  • Endothelial cell function in arteries integrates Ca2+ signaling with hyperpolarization for smooth muscle relaxation and blood flow.
  • The signaling mechanisms in lymphatic endothelium, particularly regarding Ca2+ and electrical activity, remain largely unknown.
  • Lymphatic vessels propel lymph through coordinated contractions along lymphangions.

Purpose of the Study:

  • To investigate the electrical and intracellular Ca2+ signaling properties of lymphatic endothelial cells (LECs).
  • To determine if LECs exhibit signaling pathways that facilitate lymph propulsion.
  • To compare signaling in lymphatic endothelium with that of arterial endothelium.

Main Methods:

  • Isolation of intact mouse collecting lymphatic endothelial cell tubes (LECTs).
Keywords:
TRP channelscalcium-activated K+ channelendothelium-derived hyperpolarizing factormathematical model

Related Experiment Videos

  • Intracellular microelectrode recordings to measure membrane potential.
  • Stimulation with acetylcholine (ACh) and TRPV4 channel agonists.
  • Experiments using Trpv4-/- mice and computational modeling of ion fluxes.

    • Main Results:

    • LECs exhibit a resting membrane potential of approximately -70 mV.
    • ACh and TRPV4 activation increased intracellular Ca2+ and caused significant depolarization in LECs.
    • LECs lack Ca2+-activated K+ (KCa) channels, a key feature of arterial endothelium.
    • Depolarization in LECs is mediated by Ca2+ and Na+ influx through TRPV4 channels and is not accompanied by hyperpolarization.

    Conclusions:

    • Lymphatic endothelial cells possess distinct electrical signaling properties compared to arterial endothelium.
    • The absence of endothelium-derived hyperpolarization (EDH) and the presence of depolarization in LECs may promote rapid contraction wave conduction.
    • These signaling events likely play a crucial role in efficient lymph propulsion.