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. 1982 Nov;332:299–314. doi: 10.1113/jphysiol.1982.sp014414

Effect of barbiturates on the GABA receptor of cat primary afferent neurones

H Higashi 1, S Nishi 1
PMCID: PMC1197399  PMID: 6296374

Abstract

1. The effects of the barbiturate anaesthetics, pentobarbitone and thiopentone, on the membrane properties and the γ-aminobutyric acid (GABA)-induced responses of cat primary afferent neurones were studied with intracellular recording and voltageclamp techniques.

2. At low concentrations (10-7-10-5 M) both barbiturates slightly enhanced and prolonged GABA-induced depolarizations or currents without affecting the membrane properties. At these concentrations, barbiturates have no effect on the apparent dissociation constant of the GABA-GABA receptor interaction or the reversal potential for GABA-induced depolarizations or currents.

3. At high concentrations (10-4-10-3 M) barbiturates produced a few millivolts reduction in the resting membrane potential. Voltage-clamp analysis revealed that the depolarization was associated with one of the three types of conductance change, i.e., an initial increase followed by a decrease (40% of neurones examined), only an increase (40%) and only a decrease (20%).

4. Analysis in different ionic media indicated that the depolarization with a reduced membrane resistance is associated with an increased chloride conductance and that the one with an increased membrane resistance is accompanied by a reduction in potassium conductance. Bath-application of GABA (10-3 M) or picrotoxin (10-5 M) inhibited the increase in chloride conductance but not the reduction in potassium conductance.

5. Barbiturates at these high concentrations initially caused a marked augmentation and prolongation of GABA responses; this was followed by a depression. The depressant action did not appear to be voltage-dependent. These actions of barbiturates were not accompanied by changes in the apparent dissociation constant of the GABA-current dose—response curve or the reversal potential for GABA currents. In addition, the single exponential decay of GABA current was not changed despite a marked prolongation of its decay time.

6. Picrotoxin (10-5 M) antagonized the depressant effect of barbiturates at high concentrations on GABA currents, and barbiturates (5 × 10-6 M) reduced the inhibitory action of picrotoxin (5 × 10-6 M) on the GABA-currents.

7. From all these results, it is suggested that the site of barbiturate actions on GABA-responses is mainly the allosteric site (the ionic conductance regulatory subunit) but not the agonist recognition site or the chloride channels linked with GABA receptors.

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Selected References

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