Effect of luminal acidity on the apical cation channel in rabbit esophageal epithelium

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. Serosal nystatin abolished short-circuit current (I_sc) and luminal pH titrated from pH 7.0 to pH ≤ 2.0 had no effect on I_sc. Circuit analysis at pH 2.0 showed small, but significant, increases in apical and shunt resistances. At pH < 2.0, I_sc increased whereas resistance (R_T) decreased along with an increase in fluorescein flux. The change in I_sc, but not R_T, was reversible at pH 7.4. Reducing pH from 7.0 to 1.1 with H ₂SO₄ gave a similar pattern but higher I_sc values, suggesting shunt permselectivity. A 10:1 Na⁺ gradient after nystatin increased I_sc 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. 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.