Schmidt, S.G., Malle, M.G., Nielsen, A.K., Bohr, S.S., 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.  Nat. Commun. 13(1): 2446.

FBrf0253384

Research paper

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.

PMC9068915 (PMC) (EuropePMC)