title: The role of K+ channels in colonic Cl- secretion.
abstract: Cl- secretion in the rat colonic crypt base cell (bc) requires the coordinated (a) opening of Cl- channels in the luminal membrane; (b) activation of the Na+2Cl-K+ cotransporter; (c) enhanced conductive K+ exit from the cell; and (d) increased pumping by the (Na+ + K+)-ATPase. In this study we focus on the importance of conductive K+ exit. After stimulation with the cholinergic agonist carbachol (CCH, 0.1-10 mumol/l) bc respond with a marked increase in whole cell (wc) conductance and a hyperpolarization of the membrane voltage (Vm). This is paralleled by a marked increase in the (Cl- secretory) short-circuit current (Isc) in Ussing chamber studies of the intact distal colon. Current evidence favors the view that CCH, via IP3, enhances cytosolic Ca2+ activity, and that Ca2+ increases the open probability of Cl- channels indirectly and that of K+ channels directly. After stimulation with PGE2 bc also enhance the wc conductance, but this is paralleled by a marked depolarization of Vm. Again these effects correspond to a marked increase in (Cl- secretory) Isc. The depolarization and enhanced wc conductance is partly due to the activation of Cl- channels. However, current evidence suggests that these effects on Cl- channels are paralleled by an activation of K+ channels. The chromanol 293B, by inhibiting these K+ channels specifically, abolishes PGE2-induced Cl- secretion completely, but has no effect on basal K+ conductance or on CCH-induced Cl- secretion. CCH apparently activates a Ca(2+)-dependent K+ channel with a conductance of 10-20 pS, whilst PGE2 (or cAMP) activate a much smaller K+ channel. Only the latter K+ channel can be inhibited by 293B in excised patches. Noise analysis suggests that this K+ channel has a conductance of < 3 pS and fast kinetics. The complete 293B induced inhibition of Cl- secretion caused by PGE2 can be explained by the fact that PGE2 induces a marked depolarization and that this depolarization reduces the basal K+ conductance. Current evidence suggests that this inhibition of the basal K+ conductance is caused by a depolarization induced inhibition of Ca2+ entry.
authors.affiliation: Physiologisches Institut, Albert-Ludwigs-Universität, Freiburg, FRG.
authors.forename: R
authors.initials: R
authors.lastname: Greger
authors.forename: M
authors.initials: M
authors.lastname: Bleich
authors.forename: N
authors.initials: N
authors.lastname: Riedemann
authors.forename: W
authors.initials: W
authors.lastname: van Driessche
authors.forename: D
authors.initials: D
authors.lastname: Ecke
authors.forename: R
authors.initials: R
authors.lastname: Warth
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004553:Electric Conductivity; D007425:Intracellular Membranes / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats
chemical_list: D002712:Chlorides; D015221:Potassium Channels; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium