Effect of sodium lithium and proton concentrations on the electrophysiological properties of the four mouse GABA transporters expressed in Xenopus oocytes

Tamar R. Grossman, Nathan Nelson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mouse GABA transporters belong to the family of Na+ and Cl- dependent neurotransmitter transporter. GABA transport, by these family members, was shown to be electrogenic and driven by sodium ions. It was demonstrated that, as in several other transporters, sodium binding and release by GAT1, GAT3 and BGT-1, the canine homolog of GAT2, resulted in the appearance of presteady-state currents. In this work we show that each of the four GABA transporters exhibit unique presteady-state currents when expressed in Xenopus oocytes. The properties of the presteady-state currents correspond to the transporters affinities to Na+. At 100mM GAT1 exhibited symmetric presteady-state currents at all imposed potentials, whereas GAT2 exhibited asymmetric presteady-state currents exclusively at negative imposed potentials, GAT3 or GAT4 exhibited presteady-state currents predominantly at positive imposed potentials. GABA uptake by GAT2 and GAT4 was much more sensitive to external pH than GAT1 and GAT3. Reducing the external Na+ concentration rendered the GABA uptake activity by GAT1 and GAT3 to be sensitive to pH. Lowering the external pH reduced the Na+ affinity of GAT1. Substitution of the external Na+ to Li+ resulted in the appearance of leak currents exclusively at negative potentials in Xenopus oocyte expressing GAT1 and GAT3. Low Na+ concentrations inhibited the leak currents of GAT1 but Na+ had little effect on the leak currents of GAT3. Washing of occluded Na+ in GAT1 enhanced the leak currents. Similarly addition of GABA in the presence of 80mM Li+, that presumably accelerated the release of the bound Na+, also induced the leak currents. Conversely, addition of GABA to GAT3 expressing oocytes, in the presence of 80mM Li+, inhibited the leak currents.

Original languageEnglish
Pages (from-to)431-443
Number of pages13
JournalNeurochemistry International
Volume43
Issue number4-5
DOIs
StatePublished - 2003

Funding

FundersFunder number
United States-Israel Binational Science Foundation

    Keywords

    • Lithium
    • Proton
    • Sodium

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