HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Higashi, H. Articles by Nishi, S. Search for Related Content PubMed PubMed Citation Articles by Higashi, H. Articles by Nishi, S.

Department of Physiology, Kurume University School of Medicine, Kurume, 830 Japan

1. The effects of the barbiturate anaesthetics, pentobarbitone and thiopentone, on the membrane properties and the -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 x 10^-6 M) reduced the inhibitory action of picrotoxin (5 x 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.