Inhibition of a K+ conductance by the phosphatase inhibitor calyculin A in rat distal colon.

Basal membrane permeability of epithelial cells from the lower third and the middle of rat colonic crypts is dominated by a K+ conductance as shown by ion replacement experiments. Calyculin A, an inhibitor of protein phosphatases, induced a depolarization of these cells. The depolarization was concomitant with an inhibition of membrane current. The current inhibited by calyculin A had a reversal potential identical with the theoretical K+ equilibrium potential indicating that the drug inhibits a basal K+ conductance. The efficiency of calyculin A was comparable with that of other well-known K+ channel blockers such as Ba2+, tetraethylammonium or quinine. In the intact tissue, calyculin A exerted an inhibitory action on forskolin-induced anion secretion, an effect which may be explained by the decrease in the driving force for Cl- exit after inhibition of cellular K+ conductance. Together with previous results, these data suggest an inhibition of epithelial K+ conductance by phosphorylation.