title: Cyclic AMP-dependent regulation of K+ transport in the rat distal colon.
abstract: 1. 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. 2. 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. 3. 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. 4. Efflux experiments revealed that forskolin caused a redistribution of cellular K+ efflux reducing the ratio of basolateral versus apical Rb+ efflux. 5. 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.
authors.affiliation: Institut für Veterinär-Physiologie, Universität Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Diener
authors.forename: F
authors.initials: F
authors.lastname: Hug
authors.forename: D
authors.initials: D
authors.lastname: Strabel
authors.forename: E
authors.initials: E
authors.lastname: Scharrer
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D054328:Proton Pump Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D002839:Chromans; D015221:Potassium Channels; D054328:Proton Pump Inhibitors; D012414:Rubidium Radioisotopes; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D005576:Colforsin; D012964:Sodium; D000242:Cyclic AMP; D017506:H(+)-K(+)-Exchanging ATPase