On the pharmacology of the gamma-aminobutyric acid receptors on the cuneo-thalamic relay cells of the cat

Abstract

1. gamma-Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo-thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone.2. Glycine 13+/-2 nA and GABA 20+/-2 nA were equipotent depressors of hair cells (n=22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log-current response curves. The GABA equipotent dose-ratio was 2.0+/-0.2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate.3. Although a maximal bicuculline current seldom caused a significant shift of the glycine-log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.4. Bicuculline also antagonized depressions by beta-guanidinopropionic acid, and delta-aminovaleric acid which mimicked the action of GABA.5. When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive.6. The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0.2 mg/kg).7. The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo-thalamic relay cells to be determined.