Regulation of apical and basolateral K + conductances in the rat colon

1 Apical administration of an ionophore, nystatin, and basolateral depolarization by K + were used to investigate the regulation of apical and basolateral electrogenic transport pathways for K + in the rat proximal and distal colon. 2 Administration of nystatin (100 μg ml −1 at the mucosal side), in the presence of Na + and in the presence of a serosally directed K + gradient, stimulate a large increase in short‐circuit current ( I SC ) and tissue conductance in both colonic segments. This response was composed of a pump current generated by the Na + ‐K + ‐ATPase and of a current across a quinine‐sensitive basolateral K + conductance. 3 The pump current, measured as Na + ‐dependent or scilliroside‐sensitive current in the absence of a K + gradient, was significantly greater in the distal than in the proximal colon. The pump current was unaltered by pretreatment of the tissue with forskolin (5×10 −6  mol l −1 ). 4 The current across the basolateral K + conductance, measured as current in the presence of a serosally directed K + gradient either in the absence of Na + or in the presence of scilliroside, was increased by the cholinoreceptor agonist, carbachol (5×10 −5  mol l −1 ), but inhibited by forskolin (5×10 −6  mol l −1 ). 5 Basolateral K + depolarization induced a negative I SC in both colonic segments, which was inhibited by the K + channel blocker quinine (10 −3  mol l −1 at the mucosal side), but was resistant to tetraethylammonium (5×10 −3  mol l −1 at the mucosal side). This K + current across an apical K + conductance was stimulated in both colonic segments by carbachol, whereas forskolin had no effect, although control experiments revealed that forskolin was still able to open an apical Cl − conductance under these conditions. 6 These results demonstrate that an increase in intracellular Ca 2+ concentration induced by carbachol causes an increase in the basolateral and the apical K + conductance, thereby inducing K + secretion in parallel with an indirect support for Cl − secretion due to the hyperpolarization of the cell membrane. In contrast, the dominating effect of an increase in the intracellular cyclic AMP concentration is inhibition of a basolateral K + conductance; a mechanism which might contribute to the inhibition of K + absorption.British Journal of Pharmacology (1997) 122 , 87–94; doi: 10.1038/sj.bjp.0701353