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Related Experiment Videos

Extracellular ATP regulates transcervical permeability by modulating two distinct paracellular pathways

G I Gorodeski1, J Goldfarb

  • 1Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

The American Journal of Physiology
|May 1, 1997
PubMed
Summary

Extracellular ATP causes biphasic changes in human cervical cell electrical resistance. These distinct phases, involving lateral intercellular space and tight junction resistance, are independently regulated by ATP.

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Area of Science:

  • Cell biology
  • Epithelial physiology

Background:

  • Extracellular ATP (adenosine triphosphate) influences epithelial cell function.
  • Human cervical epithelial cells exhibit changes in transepithelial electrical resistance (RTE) in response to ATP.

Purpose of the Study:

  • To investigate the roles of lateral intercellular space resistance (RLIS) and tight junctional resistance (RTJ) in ATP-induced RTE changes.
  • To differentiate the mechanisms of the acute (phase I) and delayed (phase II) responses to ATP.

Main Methods:

  • Utilized 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester to block calcium signaling and uncouple ATP-induced phases.
  • Measured RLIS and RTJ in cultured human cervical epithelial cells under control and BAPTA-treated conditions.
  • Analyzed the kinetics and magnitude of resistance changes during phase I and phase II.

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Main Results:

  • BAPTA treatment abolished phase I, indicating its dependence on cytosolic calcium.
  • Phase I involved a rapid, exponential decrease in RLIS, while phase II showed complex kinetics and primarily affected RTJ.
  • Phase I and phase II responses were found to be simultaneously and independently induced by ATP.

Conclusions:

  • ATP independently modulates both RLIS and RTJ, contributing distinctly to overall RTE changes.
  • These findings suggest ATP-mediated regulation of RLIS and RTJ are key mechanisms for controlling cervical mucus production in vivo.