The dopamine transporter antiports potassium to increase the uptake of dopamine

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 and Claus J. Loland ()
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Solveig G. Schmidt: University of Copenhagen
Mette Galsgaard Malle: University of Copenhagen
Anne Kathrine Nielsen: University of Copenhagen
Søren S.-R. Bohr: 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
Claus J. Loland: University of Copenhagen

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30154-5

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