title: Cytosolic ionized Ca2+ modulates chemical hypoxia-induced hyperpermeability in intestinal epithelial monolayers.
abstract: We reported previously that ATP depletion induced by glycolytic inhibition or cellular hypoxia increases the permeability of intestinal epithelial monolayers [N. Unno, M. J. Menconi, A. L. Salzman, M. Smith, S. Hagen, Y. Ge, R. M. Ezzell, and M. P. Fink. Am. J. Physiol. 270 (Gastrointest. Liver Physiol. 33): G1010-G1021, 1996]. In the present study, we examined the effects of the Ca2+ ionophore A-23187 or the intracellular ionized Ca2+ concentration ([Ca2+]i) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM on the permeability of enterocytic (T84) monolayers depleted of ATP by metabolic inhibition. Permeability was assessed by measuring transepithelial electrical resistance and the transepithelial flux of fluorescein sulfonic acid. Although neither A-23187 nor BAPTA-AM affected ATP depletion, A-23187 augmented, whereas BAPTA-AM ameliorated, chemical hypoxia-induced hyperpermeability. BAPTA-AM ameliorated chemical hypoxia-induced cytoskeletal derangements. Monolayers subjected to chemical hypoxia but incubated in a low (i.e., 100 microM) [Ca2+] environment showed preservation of junctional integrity, whereas voltage-dependent Ca2+ channel blockers (NiCl2 or verapamil) failed to ameliorate chemical hypoxia-induced hyperpermeability. ATP depletion induces hyperpermeability in intestinal epithelial monolayers via a [Ca2+]i-dependent mechanism. Increased [Ca2+]i under these conditions reflects leakage of Ca2+ from the extracellular milieu via a mechanism unrelated to voltage-dependent Ca2+ channels.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: N
authors.initials: N
authors.lastname: Unno
authors.forename: S
authors.initials: S
authors.lastname: Baba
authors.forename: M P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism; D007477:Ions; D008856:Microscopy, Fluorescence; D009994:Osmolar Concentration; D010539:Permeability; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007477:Ions; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D000001:Calcimycin; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D002118:Calcium