Anion selectivity and block of the small-conductance chloride channel on pancreatic duct cells.
Rat and human pancreatic duct cells have small-conductance Cl- channels in their apical plasma membranes. These channels are regulated by secretin and adenosine 3',5'-cyclic monophosphate and may function in parallel with Cl(-)-HCO3- exchangers to allow HCO3- secretion from the duct cell. Using the patch-clamp technique, we have now determined the anion permeability sequence of the channel as NO3- greater than Br- approximately I- approximately Cl- much greater than HCO3- much greater than gluconate. From this we conclude 1) that anion permeation involves a weak interaction with charged sites inside the channel pore, 2) that because of the low HCO3-/Cl- permeability ratio it is unlikely that significant amounts of HCO3- could be secreted directly via the channel, and 3) that channel permeability may determine the anion selectivity of secretion. We also show that 5-nitro-2-(3-phenylpropylamino)benzoic acid blocks the small-conductance Cl- channel, whereas 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid has no effect.
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, United Kingdom.
M A
MA
Gray
C E
CE
Pollard
A
A
Harris
L
L
Coleman
J R
JR
Greenwell
B E
BE
Argent
D000818:Animals; D000838:Anions; D001639:Bicarbonates / Q000378:metabolism; D018118:Chloride Channels; D003300:Copper / Q000172:deficiency; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology; D010183:Pancreatic Ducts / Q000502:physiology*; D051381:Rats
D000838:Anions; D001639:Bicarbonates; D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D003300:Copper