Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels.
The action of TBPS (tert-butylbicyclophosphorothionate) on spontaneous chloride channels recorded from porcine pars intermediate lobe cells in primary culture has been studied. This compound, which binds specifically to the gamma-aminobutyric acidA (GABAA) receptor complex, is known as a channel-gating (non-competitive) GABA antagonist. The present results show that TBPS reduces spontaneous chloride channel activity in a dose-dependent manner, with an IC50 equal to 55 nM, which is a value comparable to its affinity for the GABAA binding sites. Single-channel analysis revealed that TBPS affects neither the amplitude nor the open time of these spontaneous channels but prolongs the longer closed times, resulting in a dramatic decrease in opening probability.
Hamann
M
M
Laboratoire de Neuroendocrinologie Comparée (URA 98 CNRS), Strasbourg, France.
Desarmenien
M
M
Vanderheyden
P
P
Piguet
P
P
Feltz
P
P
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology*; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D018118:Chloride Channels; D002712:Chlorides; D003292:Convulsants; D008565:Membrane Proteins; C037476:tert-butylbicyclophosphorothionate