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The effect of agonists of the cyclic AMP pathway and of 293B, a chromanole‐derived K+ channel blocker, on K+ transport in the rat distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb+ in mucosa‐submucosa preparations and by patch‐clamp of crypt epithelia from isolated crypts. 293B concentration‐dependently inhibited basal and forskolin‐stimulated short‐circuit current. In isolated crypts 293B blocked a basal K+ conductance but had no effect on cyclic AMP‐evoked depolarization induced by the opening of apical Cl− channels. When the effect of cyclic AMP on Cl− conductance was prevented by substituting Cl− with gluconate, an inhibition of total cellular K+ conductance by forskolin and a membrane‐permeable cyclic AMP analogue was unmasked. Unidirectional ion flux measurements revealed that 293B suppressed the increase in JRbsm induced by forskolin. This, together with the inhibition of cyclic AMP‐induced anion secretion indicates that the drug blocks K+ channels, presumably both in the apical and the basolateral membrane. Forskolin caused not only inhibition of K+ absorption, but also stimulation of K+ secretion. The inhibition was diminished, but not blocked, in the presence of inhibitors of the apical H+‐K+‐ATPase, vanadate and ouabain. Forskolin stimulated serosal, bumetanide‐sensitive Rb+ uptake, whereas mucosal, ouabain/vanadate‐sensitive uptake remained unaffected. Efflux experiments revealed that forskolin caused a redistribution of cellular K+ efflux reducing the ratio of basolateral versus apical Rb+ efflux. These results suggest that intracellular cyclic AMP exerts its effects on K+ transport by several mechanisms: an increase in the driving force for K+ efflux due to the depolarization induced by opening of Cl− channels, a stimulation of the basolateral uptake of K+ via the Na+‐K+‐Cl−‐cotransporter, and a decrease of the ratio of basolateral versus apical K+ conductance leading to an enhanced efflux of K+ into the lumen and a reduced K+ efflux to the serosal compartment.

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