Potent block of volume-activated chloride currents in endothelial cells by the uncharged form of quinine and quinidine.
1. The effects of quinine and quinidine on the volume-activated chloride current (ICl(vol)) in cultured endothelial cells from bovine pulmonary artery were studied by use of the whole-cell patch-clamp technique. 2. At pH 7.4 both quinine and quinidine induced a fast and reversible block of ICl(vol)) with Ki values of 20 +/- 4 microM and 30 +/- 10 microM, respectively. 3. The blocking efficiency of both drugs increased dramatically with increasing extracellular pH, indicating that the blockade is mediated by the uncharged form of quinine and quinidine. 4. These results suggest a hydrophobic interaction with high affinity between volume-activated chloride channels and uncharged quinine and quinidine within the membrane bilayer of endothelial cells.
Voets
T
T
KU Leuven, Laboratorium Voor Fysiologie, Belgium.
Droogmans
G
G
Nilius
B
B
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011802:Quinidine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D000962:Antimalarials; D018118:Chloride Channels; D011803:Quinine; D011802:Quinidine