Claudin-2-dependent paracellular channels are dynamically gated

Autor: Christopher R Weber, Guo Hua Liang, Yitang Wang, Sudipto Das, Le Shen, Alan S L Yu, Deborah J Nelson, Jerrold R Turner
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: eLife, Vol 4 (2015)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.09906
Popis: Intercellular tight junctions form selectively permeable barriers that seal the paracellular space. Trans-tight junction flux has been measured across large epithelial surfaces, but conductance across individual channels has never been measured. We report a novel trans-tight junction patch clamp technique that detects flux across individual claudin-2 channels within the tight junction of cultured canine renal tubule or human intestinal epithelial monolayers. In both cells, claudin-2 channels display conductances of ~90 pS. The channels are gated, strictly dependent on claudin-2 expression, and display size- and charge-selectivity typical of claudin-2. Kinetic analyses indicate one open and two distinct closed states. Conductance is symmetrical and reversible, characteristic of a passive, paracellular process, and blocked by reduced temperature or site-directed mutagenesis and chemical derivatization of the claudin-2 pore. We conclude that claudin-2 forms gated paracellular channels and speculate that modulation of tight junction channel gating kinetics may be an unappreciated mechanism of barrier regulation.
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