Outwardly rectifying Cl- channel in guinea pig small intestinal villus enterocytes: effect of inhibitors.
Previous studies in enterocytes isolated from the villus region of small intestinal epithelium have identified a macroscopic current carried by Cl-. In this work a single-channel patch-clamp study was carried out in the same cells, and a spontaneously active, outwardly rectifying Cl- channel was identified and proposed to underlie the whole cell current. 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 calcium levels and voltage. The selectivity sequence for different anions was SCN- > I- > Br- > Cl- > F- > (gluconate, glutamate, SO4(2-)). The channel was inhibited by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), verapamil, and 4-hydroxytamoxifen (but not by tamoxifen), with potencies 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 half-maximal inhibitory concentration was 18 nM. It is proposed that this channel plays a role in transepithelial Cl- transport and certain regulatory Cl- fluxes.
Monaghan
A S
AS
Department of Child Health, Ninewells Hospital and Medical School, University of Dundee, United Kingdom.
Mintenig
G M
GM
Sepúlveda
F V
FV
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D018698:Glutamic Acid / Q000493:pharmacokinetics; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000838:Anions; D018118:Chloride Channels; D009579:Nitrobenzoates; D013629:Tamoxifen; C016601:afimoxifene; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D018698:Glutamic Acid; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D014700:Verapamil