Esophageal epithelial cells contain an apical cation channel that actively absorbs sodium ions (Na⁺). Since these channels are exposed in vivo to acid reflux, we sought the impact of high acidity on Na⁺ channel function in Ussing-chambered rabbit epithelium. RESULTS: Serosal nystatin abolished short-circuit current (Isc) and luminal pH titrated from pH 7.0 to pH 2.0 had no effect on Isc. Circuit analysis at pH 2.0 showed small, but significant, increases in apical and shunt resistances. At pH < 2.0, Isc increased while resistance (R_T) decreased along with an increase in fluorescein flux. The change in Isc, but not R_T was reversible at pH 7.4. Reducing pH from 7.0 to 1.1 with H₂SO₄ gave a similar pattern, but higher Isc values, suggesting shunt permselectivity. A 10:1 Na⁺ gradient after nystatin increased Isc by ~4 µAmps/cm² and this declined at pH 3.5 until it reached ~0.0 at pH 2.0. Impedance analysis on acid-exposed (non-nystatin-treated) tissues showed compensatory changes in apical (increase) and basolateral (decrease) resistance at modest luminal acidity that were poorly reversible at pH 2.0 and associated with declines in capacitance, a reflection of lower apical membrane area. CONCLUSIONS: In esophageal epithelium apical cation channels transport Na⁺ at gradients as low as 10:1 but do not transport H⁺ at gradients of 100,000:1 (luminal pH 2.0). Luminal acid also inhibits Na⁺ transport via the channels and abolishes it at pH 2.0. These effects on the channel may serve as a protective function for esophageal epithelium exposed to acid reflux.