Regulation of apical and basolateral K plus 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 mu g 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 x 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 x 10(-5) mol l(-1)), but inhibited by forskolin (5 x 10(-6) mol l(-1)). 5 Basolateral K+ depolarization induced a negative I-se 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 x 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 Ca2+ 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.