Differential effect of pH on sodium binding by the various GABA transporters expressed in Xenopus oocytes

Mouse GABA transporters belong to the family of Na⁺- and Cl^--dependent neurotransmitter transporters. The four GABA transporters exhibit unique presteady-state currents when expressed in Xenopus oocytes. The properties of the presteady-state currents correspond to their different affinities to Na⁺. In the presence of 20 μM GABA and at pH 7.5, the half-maximal uptake activity was 47, 120, 25 and 35 mM Na⁺ for GAT1, GAT2, GAT3 and GAT4, respectively. The appearance of presteady-state currents at positive or negative imposed potentials was in correlation with the affinity to Na⁺. Changing the external pH differentially affected the GABA uptake and the presteady-state activities of the various GABA transporters. It is suggested that protons compete with Na⁺ on its binding site; however, the proton binding is not productive and is unable to drive GABA uptake.