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Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
Published on: May 26, 2021
Claudin-16 affects transcellular Cl- secretion in MDCK cells.
Dorothee Günzel1, Salah Amasheh, Sandra Pfaffenbach
1Institut für Klinische Physiologie, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. dorothee.guenzel@charite.de
The Journal of Physiology
|June 17, 2009
Summary
Claudin-16 protein influences kidney ion transport by modulating transcellular chloride currents, not directly affecting paracellular calcium or magnesium passage. This interaction regulates magnesium and calcium absorption in the kidneys.
Area of Science:
- Nephrology
- Molecular Biology
- Cell Biology
Background:
- Claudin-16 (paracellin-1) is a tight junction protein implicated in renal magnesium and calcium transport.
- Defects in claudin-16 cause familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, suggesting a role in ion transport.
- Previous evidence on claudin-16's direct role in paracellular ion transport remains conflicting.
Purpose of the Study:
- To investigate the role of claudin-16 in paracellular ion permeability, specifically for Mg(2+) and Ca(2+).
- To examine how claudin-16 affects the driving forces for passive ion movement in kidney cells.
- To elucidate the mechanism by which claudin-16 influences renal ion absorption.
Main Methods:
- Stable transfection of MDCK-C7 cells with wild-type (wt) and mutant (R146T, T233R) claudin-16.
- Measurement of paracellular ion permeabilities to Mg(2+) and Ca(2+).
- Analysis of transcellular currents and their regulation by ion concentrations and the calcium-sensing receptor.
Main Results:
- Cells expressing wt claudin-16 showed increased paracellular Mg(2+) permeability compared to mutants and controls, but not for Ca(2+).
- Increased basolateral Mg(2+) activated a transcellular Cl(-) current, significantly enhanced in wt and T233R claudin-16 expressing cells.
- This current involved the calcium-sensing receptor, internal Ca(2+) stores, and apical Ca(2+)-activated Cl(-) channels, likely bestrophin.
Conclusions:
- Claudin-16 has a moderate direct effect on paracellular Mg(2+) permeability.
- Claudin-16 primarily regulates renal Mg(2+) and Ca(2+) absorption by governing transcellular Cl(-) currents.
- This regulation occurs through interaction with apical Ca(2+)-activated Cl(-) channels, influencing transepithelial voltage and ion driving forces.
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