Effects of zolpidem and protons on GABA-induced current in the hippocampal pyramidal neurons in the presence of penicillin

Abstract

Introduction. Type A receptors activated by gamma-aminobutyric acid (GABAAR) play an inhibitory role in the nervous system due to the generation of chlorine current (IGABA). Penicillin is a sequential blocker of the GABAAR open channel, which can inhibit dissociation of the GABA-receptor complex. This GABA site modulation suggests that the effects of competitive GABAAR modulators may change in the presence of penicillin. The aim of the study was to evaluate the effect of zolpidem, the positive competitive GABAAR modulator, and hydrogen ions (protons), the negative competitive GABAAR modulator, on IGABA in the presence of penicillin. Materials and methods. IGABA was measured on isolated pyramidal neurons of the rat hippocampus, using the patch clamp technique and fast application system. GABA, penicillin, and zolpidem were applied to the neuron for 600 msec via a lateral shift pipette. To study the effect of protons on IGABA, the GABA solution in the application pipette was acidified to pH 6.07.0. Results. The application of 1 mmol of penicillin reduced the IGABA amplitude to 67 4% of the control value. Zolpidem, with a concentration of 0.5 mol,increased the IGABA amplitude to 167 9% of the control value. When penicillin and zolpidem were co-applied, the stimulating effect of zolpidem was not observed, and the IGABA amplitude was 68 4%. Reducing the pH of the GABA solution to 7.0 or 6.0 caused the IGABA amplitude to decrease to 804 and 35 4%, respectively. The effect of protons on IGABA did not change in the presence of penicillin. Conclusion. For the first time, it has been shown that the stimulating effect of zolpidem on IGABA is cancelled out by penicillin, while the inhibitory effect of protons on IGABA is preserved.

Keywords

• gaba receptors
• penicillin
• zolpidem
• protons