Activators of protein kinase C inhibit sodium transport in A6 epithelia.

To evaluate the role of protein kinase C in sodium transport via amiloride-sensitive sodium channels, we studied the effect of activators of protein kinase C on short-circuit current in epithelia formed by A6 cells in culture. In A6 epithelia, short-circuit current is equivalent to net sodium transport and is blocked by low concentrations of amiloride added to the solution bathing the apical surface. After any of four different activators of protein kinase C [phorbol 12,13-dibutyrate (20 ng/ml), phorbol 12-myristate 13-acetate (20 ng/ml), 1-oleoyl-2-acetylglycerol (50 micrograms/ml), and mezerein (10 ng/ml)] was added to the solution bathing the apical surface, short-circuit current fell, and electrical resistance rose. Nystatin added to the apical solution reversed the inhibition of short-circuit current, indicating that activators of protein kinase C inhibited transport at amiloride-sensitive sodium channels in the apical plasma membrane. Under some conditions, the activators also stimulated amiloride-insensitive short-circuit current. The ion transport represented by the amiloride-insensitive short-circuit current appears to be the result of basal to apical transport of chloride, but this has not been established conclusively.