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

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Abstract
Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or iontophoresis were recorded using intracellular microelectrodes. Of the 12 structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. Studies determining concentration-response relationships indicated that 2-3 molecules of GABA are required to combine with the GABA receptor for activation. Bicuculline and picrotoxin each acted in a non-competitive manner to antagonize the GABA-induced membrane current. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was -23.5 .+-. 6.1 mV. EGABA was dependent on [Cl-]o [extracelluar concentration of Cl-], but independent of [Na+]o, [K+]o, or [Ca2+]o. Intracellular injection of 20 anions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, BR4-, 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 longer than that of ClO3-. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 .+-. 2.6 min. Picrotoxin did not alter this value. When foreign anions were exchanged for Cl- in the perfusion solution, the 10 anions smaller or equal to ClO3- decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 .times. control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. The 10 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.