Effect of Protons on GABAA Receptors in Central Neurons of Various Types

Whole-cell patch-clamp technique was employed to record chloride ionic current I-GABA 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 I-GABA; the effect was more pronounced on hippocampal neurons (carrying both synaptic and extrasynaptic GABA(A) receptors) than in cerebellar Purkinje cells (predominantly equipped with synaptic GABA(A) receptors). In hippocampal neurons, pharmacological isolation of extrasynaptic component from total I-GABA was performed with GABA(A) receptor antagonist gabazine (50 nM). The extrasynaptic component of I-GABA was stronger blocked by protons than total I-GABA. It was concluded that acidic medium produced more potent blocking effect on extrasynaptic GABA(A) receptors than on synaptic ones.