Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance.
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.
Kaila
K
K
Department of Zoology, University of Helsinki, Finland.
Voipio
J
J
D000818:Animals; D003400:Astacoidea; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D001826:Body Fluids / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001639:Bicarbonates; D005680:gamma-Aminobutyric Acid