Cytosolic ionized Ca2+modulates chemical hypoxia-induced hyperpermeability in intestinal epithelial monolayers

N Unno, S Baba, MP Fink - American Journal of Physiology …, 1998 - journals.physiology.org
N Unno, S Baba, MP Fink
American Journal of Physiology-Gastrointestinal and Liver …, 1998journals.physiology.org
We reported previously that ATP depletion induced by glycolytic inhibition or cellular
hypoxia increases the permeability of intestinal epithelial monolayers [N. Unno, MJ Menconi,
AL Salzman, M. Smith, S. Hagen, Y. Ge, RM Ezzell, and MP 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 …
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 μM) [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+]iunder these conditions reflects leakage of Ca2+from the extracellular milieu via a mechanism unrelated to voltage-dependent Ca2+channels.
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