Effect of γ-Aminobutyric Acid on Intracellular pH in the Crayfish Stretch-Receptor Neurone

The effect of γ-aminobutyric acid (GABA) on intracellular pH (pHi) was examined in the crayfish stretch-receptor neurone using H⁺-selective microelectrodes and a two-microelectrode voltage clamp. In the presence of 30 mmol I⁻¹ HCO₃⁻ (pH 7.4), application of GABA (0.5 mmol I⁻¹) produced a mean fall in pHi of 0.26 units. The initial rate of fall of pHi was attributable to a net influx of acid equivalents of 6.3 mmol I⁻¹ min⁻¹. In the nominal absence of HCO₃⁻, GABA had little effect on pHi. The HCO₃⁻-dependent acidosis caused by GABA was inhibited by picrotoxin (0.1 mmol I⁻¹) but not by depletion of extracellular and intracellular Cl⁻. Acetazolamide (0.1 mmol I⁻¹) decreased the rate of fall of pHi caused by a step increase in CO₂ partial pressure as well as by GABA, which indicates that the neurone contains carbonic anhydrase. In the presence of both Cl⁻ and HCO₃⁻, the reversal potential of the GABA-activated current was more positive than under nominally HCO₃⁻-free conditions. In line with this, GABA induced a marked HCO₃⁻-dependent depolarization, and this depolarizing action was enhanced in the absence of Cl⁻ so as to lead to triggering of action potentials. All these observations support the conclusion that the GABA-induced fall in pHi is due to a net efflux of HCO₃⁻ through the inhibitory anion channels.