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The Effect of Acute Hypoxia on Short-Circuit Current and Epithelial Resistivity in Biopsies from Human Colon

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Abstract

Background and Aims

In isolated colonic mucosa, decreases in short-circuit current (I SC) and transepithelial resistivity (R TE) occur when hypoxia is either induced at both sides or only at the serosal side of the epithelium. We assessed in human colon biopsies the sensitivity to serosal-only hypoxia and mucosal-only hypoxia and whether Na, K-ATPase blockade with ouabain interacts with hypoxia.

Materials and Methods

Biopsy material from patients undergoing colonoscopy was mounted in an Ussing chamber for small samples (1-mm2 window). In a series of experiments we assessed viability and the electrical response to the mucolytic, dithiothreitol (1 mmol/l). In a second series, we explored the effect of hypoxia without and with ouabain. In a third series, we evaluated the response to a cycle of hypoxia and reoxygenation induced at the serosal or mucosal side while keeping the oxygenation of the opposite side.

Results

1st series: Dithiothreitol significantly decreased the unstirred layer and I SC but increased R TE. 2nd series: Both hypoxia and ouabain decreased I SC, but ouabain increased R TE and this effect on R TE prevailed even during hypoxia. 3rd series: Mucosal hypoxia caused lesser decreases of I SC and R TE than serosal hypoxia; in the former, but not in the latter, recovery was complete upon reoxygenation.

Conclusions

In mucolytic concentration, dithiothreitol modifies I SC and R TE. Oxygen supply from the serosal side is more important to sustain I SC and R TE in biopsy samples. The different effect of hypoxia and Na, K-ATPase blockade on R TE suggests that their depressing effect on I SC involves different mechanisms.

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Acknowledgments

We thank Dr. Dino Sánchez De Simone and Dr. Jorge Izaguirre, both from the Hospital Español, and Prof. Daniel Mathus, from the Hospital Militar, for their kind collaboration for the obtention of biopsy material. Supported by a grant from the Secretaría de Ciencia y Técnica, Universidad Nacional de Cuyo, Mendoza, Argentina.

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  1. Faculty of Medical Sciences, Institute of Physiology, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina

    Graciela E. Carra, Jorge E. Ibáñez & Fernando D. Saraví

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  1. Graciela E. Carra
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  2. Jorge E. Ibáñez
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  3. Fernando D. Saraví
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Correspondence to Fernando D. Saraví.

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Carra, G.E., Ibáñez, J.E. & Saraví, F.D. The Effect of Acute Hypoxia on Short-Circuit Current and Epithelial Resistivity in Biopsies from Human Colon. Dig Dis Sci 58, 2499–2506 (2013). https://doi.org/10.1007/s10620-013-2711-0

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  • DOI: https://doi.org/10.1007/s10620-013-2711-0

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