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The dopamine transporter antiports potassium to increase the uptake of dopamine

Author

Listed:
  • Solveig G. Schmidt

    (University of Copenhagen)

  • Mette Galsgaard Malle

    (University of Copenhagen
    University of Copenhagen)

  • Anne Kathrine Nielsen

    (University of Copenhagen
    University of Copenhagen)

  • Søren S.-R. Bohr

    (University of Copenhagen
    University of Copenhagen)

  • Ciara F. Pugh

    (University of Copenhagen)

  • Jeppe C. Nielsen

    (University of Copenhagen)

  • Ida H. Poulsen

    (University of Copenhagen)

  • Kasper D. Rand

    (University of Copenhagen)

  • Nikos S. Hatzakis

    (University of Copenhagen
    University of Copenhagen)

  • Claus J. Loland

    (University of Copenhagen)

Abstract

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.

Suggested Citation

  • Solveig G. Schmidt & Mette Galsgaard Malle & Anne Kathrine Nielsen & Søren S.-R. Bohr & Ciara F. Pugh & Jeppe C. Nielsen & Ida H. Poulsen & Kasper D. Rand & Nikos S. Hatzakis & Claus J. Loland, 2022. "The dopamine transporter antiports potassium to increase the uptake of dopamine," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30154-5
    DOI: 10.1038/s41467-022-30154-5
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    References listed on IDEAS

    as
    1. Ingvar R. Möller & Marika Slivacka & Anne Kathrine Nielsen & Søren G. F. Rasmussen & Ulrik Gether & Claus J. Loland & Kasper D. Rand, 2019. "Conformational dynamics of the human serotonin transporter during substrate and drug binding," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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