GABA receptors induced in Xenopus oocytes by chick brain mRNA: evaluation of TBPS as a use-dependent channel-blocker.
Sensitivity to GABA was induced in Xenopus laevis oocytes by injection of poly(A)+ mRNA extracted from 19-day chick embryo brain. The effect of the convulsant drug t-butylbicyclophosphorothionate (TBPS) was studied on the responses to bath-applied GABA using voltage-clamp techniques. TBPS reversibly inhibited the GABA-evoked current (IGABA) in a dose-dependent manner; however, the chloride currents evoked by carbachol or serotonin, or the spontaneous chloride fluctuations, were unaffected. The onset of the block by TBPS was faster in the presence of GABA. The recovery from the block after TBPS wash-out was also agonist-stimulated. At the steady state block, TBPS showed a mixed type of inhibition: increasing the GABA concentration decreased but failed to abolish completely the inhibition by TBPS. The TBPS block was independent of the direction of the chloride flow: both inward and outward IGABA were blocked. The time course of the decay of IGABA was markedly changed in the presence of TBPS: above 40 microM GABA, this time course showed essentially two exponentials and TBPS abolished only the fast component, whereas at a low concentration (less than or equal to 4 microM), IGABA was relatively constant and uniformly reduced by TBPS. It is suggested that TBPS may stabilize a closed form of the liganded receptor-channel complex.
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002642:Chick Embryo; D002712:Chlorides / Q000378:metabolism; D005260:Female; D018756:GABA Antagonists; D007473:Ion Channels / Q000187:drug effects*; D009865:Oocytes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D002712:Chlorides; D018756:GABA Antagonists; D007473:Ion Channels; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C037476:tert-butylbicyclophosphorothionate