Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones.
1. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro-electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration-response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non-competitive manner to antagonize the GABA-induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be -23.5 plus or minys 6.1 mV. EGABA was independent upon [cl-]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, Bf4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO-3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. 9. The ten anions larger than ClO3- produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3-, indicated that this depression was non-competitive.
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D000838:Anions; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011955:Receptors, Drug / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000613:Aminobutyrates; D000838:Anions; D001640:Bicuculline; D002712:Chlorides; D010852:Picrotoxin; D011955:Receptors, Drug; D005680:gamma-Aminobutyric Acid