Chemical hypoxia increases junctional permeability and activates electrogenic ion transport in human intestinal epithelial monolayers.
BACKGROUND
The intestinal epithelial tight junction restricts the paracellular permeation of ions and nonelectrolytes. We hypothesized that this function could be altered or disrupted during cellular adenosine triphosphate (ATP) depletion (chemical hypoxia).


METHODS
T84 monolayers grown on permeable supports were studied by electrophysiologic and flux techniques. Mitochondrial and glycolytic inhibitors were used to deplete cellular ATP.


RESULTS
Transepithelial resistance to passive ion flow (R) rapidly decreased to 36% of control values with chemical hypoxia, an effect that was reversible if control conditions were restored within 1 hour. As ATP levels declined, a transient Cl- secretory current developed but disappeared as ATP levels reached 5% of control values. Both the secretory current and fall in R were abolished when ambient Cl- was replaced with gluconate but not with Br- or NO3-, or when N-methylglucamine replaced Na+. Transepithelial flux of mannitol but not inulin was increased during ATP depletion. Dual Na(+)-mannitol flux analysis confirmed that the decrease in R was due to an increase in paracellular, not transcellular, permeability. Dilution potentials indicated altered charge selectivity of the junctional pathway.


CONCLUSIONS
Chemical hypoxia in intestinal epithelial monolayers alters but does not disrupt the permselectivity properties of the junctional complex.
Matthews
J B
JB
Department of Surgery, Beth Israel Hospital, Boston, MA 02215.
Smith
J A
JA
Tally
K J
KJ
Menconi
M J
MJ
Nguyen
H
H
Fink
M P
MP
D000255:Adenosine Triphosphate / Q000502:physiology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000648:ultrastructure; D017136:Ion Transport; D010539:Permeability
D000255:Adenosine Triphosphate