BACKGROUND/AIM: Short-circuit current (Isc) and transepithelial potential difference (PD) of rat distal colon decrease during acute hypoxia and overshoot on reoxygenation. It is not known whether tonic intrinsic nervous activity may influence these responses. METHODS: Preparations lacking the submucosal plexus (islet mucosa) and preparations retaining it (mucosa-submucosa) were mounted in Ussing chambers at 37 degrees C and gassed with 95% O2-5% CO2; Isc and PD were monitored. A 5-min hypoxia with 95% N2-5% CO2 was followed by reoxygenation. The procedure was repeated in the presence of the nervous blocking agent, tetrodotoxin (10(-6)M) in the serosal side of the chamber. RESULTS: In the isolated mucosa (n = 10) hypoxia reduced Isc by -55 +/- 5% and PD by -54 +/- 6% below baseline; reoxygenatory overshoots were, respectively, +60 +/- 17% and +/- 16%. Tetrodotoxin slightly and transiently reduced baseline Isc (-16 +/- 2%) and PD (-14 +/- 3%), with a small resistivity increase. It did not significatively modify the responses to responses to either hypoxia or reoxygenation. In mucosa-submucosa preparations (n = 9) hypoxia reduced Isc (-54 +/- 8%) and PD (-61 +/- 4%). On reoxygenation Isc and PD were increased, respectively, +30 +/- 5% and +19 +/- 6% over baseline. Tetrodotoxin reduced baseline Isc (-59.6 +/- 5%) and PD (61.3 +/- 6%). It enhanced hypoxic Isc and PD decreases (-80 +/- 5%), but not the reoxygenatory overshoots. CONCLUSIONS: 1) Tetrodotoxin affects baseline Isc and PD more intensely in submucosal plexus innervated preparations than in the isolated mucosa. 2) The epithelial electrical response to acute hypoxia appears to be modulated by tonic neural activity.