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bioRxiv · 10.1101/2021.03.11.434931

Handling of intracellular K + determines voltage dependence of plasmalemmal monoamine transporter function

Sandtner, W.·Bhat, S.·Niello, M.·Schicker, K.·Pifl, C.·Sitte, H. H.·Freissmuth, M.
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Abstract

The concentrative power of the transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT) is thought to be fueled by the transmembrane Na+ gradient, but it is conceivable that they can also tap other energy sources, e.g. membrane voltage and/or the transmembrane K+ gradient. We address this by recording uptake of endogenous substrates or the fluorescent substrate APP+ ((4-(4-dimethylamino)phenyl-1-methylpyridinium) under voltage control in cells expressing DAT, NET or SERT. We show that DAT and NET differ from SERT in intracellular handling of K+. In DAT and NET, substrate uptake was voltage-dependent due to the transient nature of intracellular K+ binding, which precluded K+ antiport. SERT, however, antiports K+ and achieves voltage-independent transport. Thus, there is a trade-off between maintaining constant uptake and harvesting membrane potential for concentrative power, which we conclude to occur due to subtle differences in the kinetics of co-substrate ion binding in closely related transporters.

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Sandtner, W., Bhat, S., Niello, M., Schicker, K., Pifl, C., Sitte, H. H., Freissmuth, M.. 2021-03-11. Handling of intracellular K + determines voltage dependence of plasmalemmal monoamine transporter function. https://doi.org/10.1101/2021.03.11.434931

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