OUTWARDLY RECTIFYING CL- CHANNEL IN GUINEA-PIG SMALL-INTESTINAL VILLUS ENTEROCYTES - EFFECT OF INHIBITORS

Previous studies in enterocytes isolated from the villus region of sma ll intestinal epithelium have identified a macroscopic current carried by Cl-. In this work a single-channel patch-clamp study was carried o ut in the same cells, and a spontaneously active, outwardly rectifying Cl- channel was identified and proposed to underlie the whole cell cu rrent. The channel had conductances of 62 and 19 pS at 80 and -80 mV, respectively, in symmetrical Cl- solutions in excised patches. Similar activity was seen in cell-attached patches, but only outward currents could be discerned in this configuration. The activity of the channel , measured as open probability, was independent of intracellular calci um levels and voltage. The selectivity sequence for different anions w as SCN- > I- > Br- > Cl- > F- > (gluconate, glutamate, SO42-). The cha nnel was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPP B), verapamil, and 4-hydroxytamoxifen (but not by tamoxifen), with pot encies similar to those observed for Cl- channels previously described in other cells. Inhibition by trinitrophenyladenosine 5'-triphosphate was also observed but only at depolarized potentials. At 50 mV the ha lf-maximal inhibitory concentration was 18 nM. It is proposed that thi s channel plays a role in transepithelial Cl- transport and certain re gulatory Cl- fluxes.