A CHROMANOL TYPE OF K-MEDIATED BUT NOT CARBACHOL-MEDIATED CL- SECRETION IN RAT AND RABBIT COLON( CHANNEL BLOCKER INHIBITS FORSKOLIN)

In a previous study [Lohrmann et al: Pflugers Arch Eur J Physiol 1995; 429:517-530] we have shown that chromanol K+ channel blockers inhibit Cl- secretion in rabbit colon. Their effect was easily demonstrable af ter stimulation by hormones acting through increases of cytosolic cAMP . The present study was undertaken to test in more detail the mechanis m of action of one of these compounds (293 B). Two types of studies we re performed: Ussing chamber experiments in rabbit distal colon and wh ole cell patch clamp studies in the isolated in vitro perfused rat col onic crypts. Carbachol (CCH, 100 mu mol/l) enhanced Cl- secretion, qua ntified as equivalent short circuit current (I-sc), in rabbit colon si gnificantly more than did prostaglandin E(2) (PGE(2)). In whole cell p atch clamp studies in rat colonic crypt cells from the base, CCH hyper polarized the membrane voltage (V-m) and enhanced whole cell conductan ce (G(m)). In agreement with previous impalement studies, 10 mu mol/l 293 B depolarized V-m in forskolin-treated rat colonic crypt base cell s even further and reduced G(m). In Ussing chamber experiments in rabb it colon, 293 B abolished the I-sc induced by PGE(2). CCH, in the cont inued presence of 293 B, still induced a large I-sc. These data indica te that 293 B specifically inhibits the forskolin- but not the CCH-ind uced Cl- secretion, and supports our previous conclusion that this cla ss of substances inhibits a cAMP-regulated K+ conductance.