Quinine inhibits chloride and nonselective cation channels in isolated rat distal colon cells.
Isolated cells from rat distal colon were investigated with the patch-clamp technique. In cell-attached and cell-excised patches (inside-out) single chloride channels with outward-rectifying properties were observed. In excised patches the single-channel conductance g was 47 +/- 5 pS at positive and 22 +/- 2 pS at negative clamp potentials (n = 6). The Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 10 microM) induced fast closing events, whereas 10 microM of 3',5-dichlorodiphenylamine-2-carboxylic acid (DCDPC) had no effect when applied to the cytosolic side. Quinine in the bath inhibited the Cl- channel by reducing its single-channel amplitude and increased open channel noise. With 0.1 mM the current amplitude decreased by 54% and with 1 mM quinine by 67%. Ca2(+)-dependent nonselective cation channels where observed after excision of the membrane patch. This channel was completely and reversibly inhibited by 100 microM DCDPC. Application of 1 mM quinine to the bath induced flickering and reduced the open-state probability from 0.94 to 0.44. In summary, besides its well established effects on K+ channels, quinine also inhibits nonselective cation channels and chloride channels by inducing fast closing events.
Gögelein
H
H
Max-Plack-Institut für Biophysik, Frankfurt/Main, F.R.G.
Capek
K
K
D000818:Animals; D018118:Chloride Channels; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000502:physiology*; D009579:Nitrobenzoates / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D018118:Chloride Channels; D007473:Ion Channels; D008565:Membrane Proteins; D009579:Nitrobenzoates; D015221:Potassium Channels; C059537:3',5-dichlorodiphenylamine-2-carboxylic acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D004159:Diphenylamine; D011803:Quinine