Low doses of ethanol have Ca²⁺ ionophore-like effects on apical membrane potential of in vitro Necturus antrum

The effects of low doses of luminal ethanol on the amiloride-sensitive apical membrane potential of Necturus antral mucosa were studied using conventional microelectrode techniques. Luminal ethanol (0.250-4.0% vol/vol) caused a dose-dependent hyperpolarization of the apical membrane potential (V(mc)), an increase in transepithelial resistance (R(t)) and resistance ratio (R(a)/R(b)), and a decrease in transepithelial potential (V(ms)). Luminal amiloride (100 μM) to 4% ethanol-treated antra did not cause any additional hyperpolarization of V(mc). Compared with luminal 2% ethanol-Ringer, an equivalent osmotic mannitol solution depolarized V(mc) and basolateral potential (V(cs)), decreased R(t) and R(a)/R(b), and increased V(ms). A single dose of 0.50% ethanol attenuated the effects of a second 2% ethanol exposure on V(mc). No change in periodic acid-Schiff (PAS)-positive mucous granule content could be found between control and 2% ethanol-treated antra. The Ca²⁺ ionophores A23187 or ionomycin (0.25-5.0 μM) dose dependently hyperpolarized the V(mc) and V(cs), increased R(t) and R(a)/R(b), and decreased V(ms). Luminal Ca²⁺-free Ringer had no effect on luminal 2.00% ethanol-induced changes in membrane potentials or resistances. Pretreatment with BAPTA blocked by ~70 and 55% the V(mc) hyperpolarization of 2 and 4% ethanol, respectively. Pretreatment with ruthenium red (10-50 μM) also dose dependently reduced the 2% ethanol-induced changes in V(mc). The data indicate that 1) low doses of luminal ethanol and Ca²⁺ ionophores have similar effects on Necturus gastric antral membrane potentials and resistances, 2) ethanol-induced hyperpolarizations of the V(mc) are partially mediated through an alteration in intracellular Ca²⁺, and 3) low doses of luminal ethanol do not cause the release of antral epithelial mucous granules at the time when significant changes are occurring in the V(mc).