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Gaba receptors induced in xenopus oocytes by chick brain messenger rna evaluation of tbps as a use dependent channel blocker



Gaba receptors induced in xenopus oocytes by chick brain messenger rna evaluation of tbps as a use dependent channel blocker



Molecular Brain Research 2(1): 21-32



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 .mu.M GABA, this time course showed essentially two exponentials and TBPS abolished only the fast component, whereas at a low concentration (.ltoreq. 4 .mu.M), 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.

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