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Elevated Intracellular Calcium Transiently Increases Tight Junction Na+ Conductance in Human Airway Epithelia
Author(s) -
Flynn Andrea,
Itani Omar,
Welsh Michael
Publication year - 2008
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.22.2_supplement.132
Subject(s) - paracellular transport , histamine , tight junction , ionomycin , chemistry , intracellular , ion transporter , histamine h1 receptor , biophysics , adherens junction , apical membrane , microbiology and biotechnology , medicine , endocrinology , biology , receptor , antagonist , biochemistry , cell , cadherin , membrane , permeability (electromagnetism)
Ions can flow across airway epithelia through cells or between cells through the paracellular pathway. Tight junctions determine paracellular conductance (Gp) and ion selectivity. Earlier work showed that histamine added to airway epithelia can release adherens junctions. Here we asked if histamine also regulates tight junctions. We found that histamine rapidly and transiently increased Gp and Na + selectivity relative to Cl − (pNa/pCl) from 1.22 to 1.69. Paracellular Na + conductance increased from 0.39 to 0.75 mS/cm 2 ; Cl − conductance showed a smaller increase from 0.32 to 0.44 mS/cm 2 . The histamine H 1 receptor antagonist pyrilamine, but not the H 2 antagonist cimetidine, prevented the Gp increase. The H 1 receptor primarily utilizes Ca 2+ as a second messenger. Preventing an increase in intracellular Ca 2+ with BAPTA‐AM or thapsigargin blocked the effect of histamine on Gp and pNa/pCl. Conversely, ionomycin, a Ca 2+ ionophore reproduced the effect of histamine, increasing Gp and pNa/pCl. In contrast, cAMP agonists failed to reproduce the histamine effect. We also examined tight junction integrity by applying lanthanum nitrate to the apical surface of airway epithelia and found that histamine transiently increased lanthanum access to the intercellular space. These data indicate that histamine signaling through the H 1 receptor increases intracellular Ca 2+ to increase tight junction Na + conductance. Our results suggest that just as ion flow through the cellular pathway is regulated, the paracellular pathway can be acutely regulated, probably to provide a pathway for counter ions to flow between the cells.