Effect of Protons on GABA A Receptors in Central Neurons of Various Types

Whole-cell patch-clamp technique was employed to record chloride ionic current IGABA evoked by fast (600 msec) application of GABA to hippocampal pyramidal neurons and cerebellar Purkinje cells isolated from rat brain. GABA solution in the application pipette was either neutral (pH 7.4) or acidic (pH 7.0 or 6.0). Application of protons to neurons causes a rapid, reversible, and dose-dependent decrease in the amplitude of IGABA; the effect was more pronounced on hippocampal neurons (carrying both synaptic and extrasynaptic GABAA receptors) than in cerebellar Purkinje cells (predominantly equipped with synaptic GABAA receptors). In hippocampal neurons, pharmacological isolation of extrasynaptic component from total IGABA was performed with GABAA receptor antagonist gabazine (50 nM). The extrasynaptic component of IGABA was stronger blocked by protons than total IGABA. It was concluded that acidic medium produced more potent blocking effect on extrasynaptic GABAA receptors than on synaptic ones.