Claudin-2-dependent paracellular channels are dynamically gated
- The University of Chicago, United States
- Lupin Research Park, India
- University of Kansas Medical Center, United States
Abstract
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.
Article and author information
Author details
Reviewing Editor
- Fiona M Watt, King's College London, United Kingdom
Version history
- Received: July 6, 2015
- Accepted: November 12, 2015
- Accepted Manuscript published: November 14, 2015 (version 1)
- Version of Record published: February 2, 2016 (version 2)
Copyright
© 2015, Weber et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Claudin-2-dependent paracellular channels are dynamically gated
eLife 4:e09906.
https://doi.org/10.7554/eLife.09906
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