Claudin-2-dependent paracellular channels are dynamically gated

Elife. 2015 Nov 14;4:e09906. doi: 10.7554/eLife.09906.


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.

Keywords: barrier function; biophysics; cell biology; epithelium; human; intestine; ion channel; patch clamp; structural biology; tight junction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport*
  • Cell Line
  • Claudin-2 / metabolism*
  • Dogs
  • Epithelial Cells / physiology*
  • Humans
  • Patch-Clamp Techniques
  • Tight Junctions / metabolism*


  • Claudin-2