Acute regulation of tight junction ion selectivity in human airway epithelia

Andrea N Flynn; Omar A Itani; Thomas O Moninger; Michael J Welsh

doi:10.1073/pnas.0813393106

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Acute regulation of tight junction ion selectivity in human airway epithelia

Journal article

Open access

Peer reviewed

Acute regulation of tight junction ion selectivity in human airway epithelia

Andrea N Flynn, Omar A Itani, Thomas O Moninger and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.106(9), pp.3591-3596

03/03/2009

DOI: 10.1073/pnas.0813393106

PMCID: PMC2638737

PMID: 19208806

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Abstract

Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La(3+) movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na(+) conductance, with a smaller increase in Cl(-) conductance. The increase was mediated by histamine H(1) receptors and depended on an increase in intracellular Ca(2+) concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport.

Tight Junctions - metabolism

Microscopy, Electron, Transmission

Epithelial Cells - metabolism

Humans

Cells, Cultured

Epithelial Cells - ultrastructure

Sodium - metabolism

Ions - metabolism

Tight Junctions - ultrastructure

Histamine - metabolism

Receptors, Histamine - metabolism

Protein Isoforms - metabolism

Biological Transport

Respiratory System - metabolism

Respiratory System - ultrastructure

Lanthanum - metabolism

Membrane Proteins - metabolism

Details

Title: Subtitle: Acute regulation of tight junction ion selectivity in human airway epithelia
Creators: Andrea N Flynn - Howard Hughes Medical Institute, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Omar A Itani
Thomas O Moninger
Michael J Welsh
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.106(9), pp.3591-3596
DOI: 10.1073/pnas.0813393106
PMID: 19208806
PMCID: PMC2638737
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: HL61234 / NHLBI NIH HHS P50 HL061234 / NHLBI NIH HHS Howard Hughes Medical Institute P01 HL051670 / NHLBI NIH HHS HL51670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 03/03/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
Record Identifier: 9984020755202771

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