gamma-Aminobutyric acid (GABA) removal from the synaptic cleft: a postsynaptic event?

In the present commentary we discuss the adequacy of Na+ transport-coupled presynaptic gamma-aminobutyric acid (GABA) uptake systems for the removal of GABA from the synaptic cleft. This discussion is based on the accepted stoichiometry for GABA presynaptic internalization, GABAout + 3Na+out + K+in in equilibrium GABAin + 3Na+in + K+out, on the parameters reported in the literature for typical synaptosomal preparations, and on the assumption that GABA removal must be a quick event (less than or equal to 2 msec), as derived from electrophysiological studies. On these bases, we have developed a calculation in order to evaluate the time course of synaptic cleft GABA removal by presynaptic systems and ended up with an overall value (t approximately 0.3 sec) which does not fit with the data derived from electrophysiological recordings. Moreover, we calculated that if such systems had the function of removing GABA within 2 msec, as it should be, a large depolarization would be brought about in GABAergic boutons, resulting ultimately in further GABA release. These considerations together with biochemical and pharmacological experimental results seem to exclude that presynaptic uptake systems have the function of removing GABA from the synaptic cleft. Our experimental data on the ability of a GABA-acceptive postsynaptic membrane (Deiters' neuron membrane) to transport GABA indicate that this system may have the correct characteristics for removing the neurotransmitter. This refers to both the kinetics and the electrophysiological consequences of the phenomenon.