Modulation by extracellular pH of the activity of GABAA receptors on rat cerebellum granule cells.

The Cl- currents activated by GABA via GABAA receptors in rat cerebellum granule cells in culture were studied by whole-cell patch-clamp. These currents were measured at various extracellular pH. The currents activated by 100 microM GABA, both the peak and the steady-state component, increase at acidic pH's and decrease at basic pH's. The transition point being at around 7.7. Interestingly, passing from pH 7.4 to 6.4 the GABA dose-response curve indicates that the increases in the peak current are related to an augmented maximal current. The increases in the steady-state component are mainly due to a higher affinity of the receptors for the neurotransmitter and disappear at saturating [GABA]. The study of the I-V curves for the GABA activated peak Cl- currents at pH 6.4, 7.4 and 8.4 reveals linearity in the latter instance. However, an outward rectification is present at the two more acidic pH's. This fact suggests that the protonation of basic amino acids at the acid pH does involve rectification of Cl- channel conductance. Overall, the data indicate that slight changes in in situ extracellular pH may have profound influences on GABAA receptor function.