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Claudins influence the number of small paracellular pores
Author(s) -
Anderson James M,
Holmes Jennifer,
Bridges Arlene,
Gookin Jody,
Coccaro Maria,
Van Itallie Christina M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a190-b
Subject(s) - paracellular transport , claudin , occludin , tight junction , chemistry , biophysics , ileum , permeability (electromagnetism) , caco 2 , cell , biochemistry , biology , membrane
Tight junctions (TJ) create charge and size‐selective barriers for solutes in the paracellular pathway. The large claudin family determines ionic selectivity, however, the basis of size discrimination remains unknown. The purpose of our study was to compare the TJ size selectivity for uncharged solutes among several cell types and to determine whether claudins influence this parameter. We simultaneously determined the permeability (P app ) for a series of 22 polyethylene glycols (PEG) ranging in radius from ≈ 2.5‐7 Å across cultured monolayers of renal tubular (LLC‐PK 1 , MDCK II, MDCK C7), and intestinal (Caco‐2) cells and porcine ileum. PEGs were quantified by post‐flux labeling with 1‐napthylisocyanate followed by HPLC‐fluorescence detection. P app showed a size discrimination extrapolating to an apparent pore radius of about 4 Å in all cell types and intestine. However, the number of pores varied widely among cell types and was unrelated to transepithelial electrical resistance (TEER). A second smaller capacity pathway was size‐independent. Inducible expression of claudin‐2 or 18, but not occludin, increased the number of small pores in MDCK II cells. Although claudins have previously been shown to regulate paracellular movement of charged ions and thus TEER, these new results are consistent with the idea that these same claudin pores also form a high capacity pathway for small uncharged solutes. (NIH DK45134, DK070883 )