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Cyclic AMP‐dependent regulation of K + transport in the rat distal colon
Author(s) -
Diener M.,
Hug F.,
Strabel D.,
Scharrer E.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15563.x
Subject(s) - forskolin , ouabain , vanadate , chemistry , efflux , biophysics , apical membrane , ion transporter , medicine , endocrinology , bumetanide , membrane potential , depolarization , intracellular , channel blocker , epithelial polarity , stimulation , biology , biochemistry , membrane , calcium , sodium , organic chemistry
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 J Rb sm 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.