Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance

Abstract

Synaptic inhibition mediated by γ-aminobutyric acid (GABA) is known to involve opening of receptor-gated chloride channels^1–3. Recent evidence indicates that these channels also show a significant permeability to the physiologically important bicarbonate anion⁴. In all the excitable cells studied to date, the intracellular pH (pH_i) is higher than would be predicted from a passive distribution of H⁺ ions^5–9, and consequently there is an outwardly directed electrochemical driving force for HCO₃⁻. In the presence of CO₂/HCO₃⁻ therefore, activation of GABA-gated channels could give rise to a significant efflux of bicarbonate, leading to a fall in postsynaptic pH_i. We have examined the influence of GABA on pH_i in crayfish skeletal muscle and we find that in the presence of CO₂, GABA induces a dramatic fall in pH_i which is coupled to an alkalosis at the extracellular surface. This fall in pH_i and the extracellular alkalosis are attributable to a GABA-activated, picrotoxin-sensitive HCO₃⁻-conductance. In view of the sensitivity of ion channels¹⁰ and intracellular ion concentrations^5–9 to changes in pH_i, a GABA-induced postsynaptic acidosis could prove to be important in the modulation of inhibitory transmission.