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

Abstract

Synaptic inhibition mediated by gamma-aminobutyric acid (GABA) is known to involve opening of receptor-gated chloride channels. Recent evidence indicates that these channels also show a significant permeability to the physiologically important bicarbonate anion. In all the excitable cells studied to date, the intracellular pH (pHi) is higher than would be predicted from a passive distribution of H+ ions, 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 pHi. We have examined the influence of GABA on pHi in crayfish skeletal muscle and we find that in the presence of CO2, GABA induces a dramatic fall in pHi which is coupled to an alkalosis at the extracellular surface. This fall in pHi and the extracellular alkalosis are attributable to a GABA-activated, picrotoxin-sensitive HCO3--conductance. In view of the sensitivity of ion channels and intracellular ion concentrations to changes in pHi, a GABA-induced postsynaptic acidosis could prove to be important in the modulation of inhibitory transmission.