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Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
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Effect of claudins 6 and 9 on paracellular permeability in MDCK II cells

David Sas1, Mingchang Hu, Orson W Moe

  • 1Dept. of Pediatrics, U.T. Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235, USA.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|September 12, 2008
PubMed

Insights

Neonatal proximal tubules exhibit lower chloride permeability and higher resistance due to specific claudin proteins. This study characterizes claudins 6 and 9 in a cell model, revealing their role in these maturational changes.

Area of Science:

  • Nephrology
  • Cell Biology
  • Physiology

Background:

  • Neonatal proximal tubules have distinct functional characteristics compared to adult tubules, including lower chloride permeability and higher electrical resistance.
  • These differences are hypothesized to stem from maturational changes in the epithelial tight junction.
  • Claudins, a family of tight junction proteins, regulate paracellular permeability, and specific isoforms (claudins 6 and 9) are present in neonatal tubules and decrease with maturation.

Purpose of the Study:

  • To investigate the functional impact of claudins 6 and 9 on epithelial permeability and resistance.
  • To determine if claudin expression changes correlate with the observed functional differences in the neonatal proximal tubule.

Main Methods:

  • Madin-Darby canine kidney II (MDCK II) cells were transfected to express claudins 6 and 9.
  • Electrophysiological studies were conducted to assess transepithelial resistance and ion permeability (P(Na)/P(Cl), P(HCO3)/P(Cl)).

Main Results:

  • Expression of claudins 6 and 9 in MDCK II cells led to a significant increase in transepithelial electrical resistance.
  • Claudin 6 and 9 expression resulted in decreased chloride permeability.
  • A decrease in the relative sodium-to-chloride permeability (P(Na)/P(Cl)) and bicarbonate-to-chloride permeability (P(HCO3)/P(Cl)) was observed.

Conclusions:

  • Claudins 6 and 9 are characterized in a cell model, demonstrating their role in regulating epithelial barrier properties.
  • These findings provide a cellular mechanism explaining the lower chloride permeability and higher resistance of the neonatal proximal tubule compared to the adult.
  • Claudin expression is a key factor in the functional maturation of the proximal tubule.

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