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.