Na+ channel blockers inhibit voltage-dependent intracellular pH changes in principal cells of frog (Rana pipiens) skin.

ABSTRACT

1. The relationship between Va and pHi was studied with double-barrelled microelectrodes in principal cells of frog skin (Rana pipiens) when (i) the transepithelial potential (Vt) was clamped at different values of Vt and (ii) when the pH of the apical solution was altered. 2. Under all conditions examined here, depolarization of Va was associated with an increase in pHi and hyperpolarization of Va was accompanied by a decrease in pHi. However, the changes in the basolateral cell membrane potential occurred, either in the same or opposite direction to that of Va depending on the conditions. 3. The voltage-dependent changes in pHi were not affected by H+ transport inhibitors or the complete removal of Na+, Cl- and HCO3- but were effectively inhibited by the application of amiloride (10(-4) M) or benzamil (10(-6)M) on the apical side. 4. A decrease in pH of the apical solution hyperpolarized Va and decreased pHi, an effect that was significantly attenuated when benzamil was present on the apical side. 5. The results indicate the presence of an H+ and/or OH- conductive pathway in the apical cell membrane of the principal cells. The effect of Na+ channel blockers suggests that this pathway proceeds through the apical Na+ channels.