Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones

J Physiol. 1978 Feb;275:263-82. doi: 10.1113/jphysiol.1978.sp012189.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminobutyrates / pharmacology*
  • Animals
  • Anions
  • Bicuculline / pharmacology
  • Cats
  • Cell Membrane Permeability / drug effects
  • Chlorides / pharmacology
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • Female
  • In Vitro Techniques
  • Male
  • Membrane Potentials / drug effects
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology*
  • Picrotoxin / pharmacology
  • Receptors, Drug / physiology
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Aminobutyrates
  • Anions
  • Chlorides
  • Receptors, Drug
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • Bicuculline