The dopamine transporter antiports potassium to increase the uptake of dopamine

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The dopamine transporter antiports potassium to increase the uptake of dopamine. / Schmidt, Solveig G; Malle, Mette Galsgaard; Nielsen, Anne Kathrine; Bohr, Søren S-R; Pugh, Ciara F; Nielsen, Jeppe C; Poulsen, Ida H.; Rand, Kasper D; Hatzakis, Nikos S; Loland, Claus J.

In: Nature Communications, Vol. 13, No. 1, 2446, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Schmidt, SG, Malle, MG, Nielsen, AK, Bohr, SS-R, Pugh, CF, Nielsen, JC, Poulsen, IH, Rand, KD, Hatzakis, NS & Loland, CJ 2022, 'The dopamine transporter antiports potassium to increase the uptake of dopamine', Nature Communications, vol. 13, no. 1, 2446. https://doi.org/10.1038/s41467-022-30154-5

APA

Schmidt, S. G., Malle, M. G., Nielsen, A. K., Bohr, S. S-R., Pugh, C. F., Nielsen, J. C., Poulsen, I. H., Rand, K. D., Hatzakis, N. S., & Loland, C. J. (2022). The dopamine transporter antiports potassium to increase the uptake of dopamine. Nature Communications, 13(1), [2446]. https://doi.org/10.1038/s41467-022-30154-5

Vancouver

Schmidt SG, Malle MG, Nielsen AK, Bohr SS-R, Pugh CF, Nielsen JC et al. The dopamine transporter antiports potassium to increase the uptake of dopamine. Nature Communications. 2022;13(1). 2446. https://doi.org/10.1038/s41467-022-30154-5

Author

Schmidt, Solveig G ; Malle, Mette Galsgaard ; Nielsen, Anne Kathrine ; Bohr, Søren S-R ; Pugh, Ciara F ; Nielsen, Jeppe C ; Poulsen, Ida H. ; Rand, Kasper D ; Hatzakis, Nikos S ; Loland, Claus J. / The dopamine transporter antiports potassium to increase the uptake of dopamine. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{5132c7e10221424fb471a7377bfa8232,
title = "The dopamine transporter antiports potassium to increase the uptake of dopamine",
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.",
keywords = "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",
author = "Schmidt, {Solveig G} and Malle, {Mette Galsgaard} and Nielsen, {Anne Kathrine} and Bohr, {S{\o}ren S-R} and Pugh, {Ciara F} and Nielsen, {Jeppe C} and Poulsen, {Ida H.} and Rand, {Kasper D} and Hatzakis, {Nikos S} and Loland, {Claus J}",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-30154-5",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - The dopamine transporter antiports potassium to increase the uptake of dopamine

AU - Schmidt, Solveig G

AU - Malle, Mette Galsgaard

AU - Nielsen, Anne Kathrine

AU - Bohr, Søren S-R

AU - Pugh, Ciara F

AU - Nielsen, Jeppe C

AU - Poulsen, Ida H.

AU - Rand, Kasper D

AU - Hatzakis, Nikos S

AU - Loland, Claus J

N1 - © 2022. The Author(s).

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Animals

KW - Dopamine/metabolism

KW - Dopamine Plasma Membrane Transport Proteins/metabolism

KW - Drosophila/metabolism

KW - Ion Transport

KW - Ions/metabolism

KW - Neurotransmitter Agents/metabolism

KW - Potassium/metabolism

KW - Serotonin Plasma Membrane Transport Proteins/metabolism

KW - Sodium/metabolism

KW - Symporters/metabolism

U2 - 10.1038/s41467-022-30154-5

DO - 10.1038/s41467-022-30154-5

M3 - Journal article

C2 - 35508541

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2446

ER -

ID: 305946701