A study is performed of the effect of the convulsants picrotoxin and bicucuUine, blockers of GABA-dependent C1--conductivity, on the rate of desensitization of muscimol-induced ~6C1-entry into synaptoneurosomes isolated from rat cortex. Both picrotoxin and bicuculline, despite the difference in the mechanisms of inhibition of the GABA receptor/C1-ionophore complex, markedly reduce the rate of desensitization. However, the initial moment of the action of both convulsants is characterized by inhibition of C1-transport alone, without a drop of the rate of desensitization.Key Words: desensitization; picrotoxin; bicuculline; synaptoneurosomes The GABA receptor/C1-ionophore complex is one of the most important molecular structures of preand postsynaptic membranes. Binding of GABA or its agonists (in particular, muscimol) with the GABA receptor opens up the coupled C1-channel and leads to a transient increase of the C1-permeability of neuronal membranes and, correspondingly, to spike inhibition. Long-term action of the transmitter results in desensitization of the receptor/ionophore complex, i.e., in a decrease of GABA-dependent C1-permeability [2,3].In our previous study we showed that pentylenetetrazole inhibition of muscimol-dependent 36C1 entry into synaptoneurosomes is accompanied by a considerable delay of desensitization. Here we report on experiments with the classic blockers of the GABA receptor/C1-ionophore complex bicuculline and picrotoxin, which act through different mechanisms. Bicuculline inhibits binding of GABA with the GABA receptor in a competitive manner MATERIALS AND METHODSIn our experiments we used the methods described earlier [1] with some modifications.White random-bred male rats weighing 180-200 g were decapitated, and the cerebral cortex was removed and homogenized manually (5 frictions) at 0-4~ in a glass homogenizer with a Teflon pestle in Krebs-Ringer medium containing (in mM): 145 NaC1, 5 KC1, 1 MgSO 4, 1 CaC 89 10 glucose, and 10 HEPES, pH 7.4 (20~ 15 ml/g tissue). The homogenate was sequentially •tered through 300-, 99-, 60-, and 27-~t capron sieves (Rakhmanov plant, Russia). The filtrate was centrifuged at 2700 g for 5 min, resuspended in the same volume of KrebsRinger medium, and recentrifuged under the same conditions. After the second centrifugation the pellet was suspended in Krebs-Ringer solution so that the final concentration of synaptoneurosomes was 4