The dopamine transporter antiports potassium to increase the uptake of dopamine

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The dopamine transporter facilitates dopamine reuptake from the extracellular space to terminate neurotransmission. The transporter belongs to the neurotransmitter:sodium symporter family, which includes transporters for serotonin, norepinephrine, and GABA that utilize the Na+ gradient to drive the uptake of substrate. Decades ago, it was shown that the serotonin transporter also antiports K+, but investigations of K+-coupled transport in other neurotransmitter:sodium symporters have been inconclusive. Here, we show that ligand binding to the Drosophila- and human dopamine transporters are inhibited by K+, and the conformational dynamics of the Drosophila dopamine transporter in K+ are divergent from the apo- and Na+-states. Furthermore, we find that K+ increases dopamine uptake by the Drosophila dopamine transporter in liposomes, and visualize Na+ and K+ fluxes in single proteoliposomes using fluorescent ion indicators. Our results expand on the fundamentals of dopamine transport and prompt a reevaluation of the impact of K+ on other transporters in this pharmacologically important family.

Original languageEnglish
Article number2446
JournalNature Communications
Issue number1
Number of pages12
Publication statusPublished - 2022

Bibliographical note

© 2022. The Author(s).

    Research areas

  • Animals, Dopamine/metabolism, Dopamine Plasma Membrane Transport Proteins/metabolism, Drosophila/metabolism, Ion Transport, Ions/metabolism, Neurotransmitter Agents/metabolism, Potassium/metabolism, Serotonin Plasma Membrane Transport Proteins/metabolism, Sodium/metabolism, Symporters/metabolism

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