Handling of intracellular K+ determines voltage dependence of plasmalemmal monoamine transporter function
- Medical University of Vienna, Austria
- University of Vienna, Austria
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2,3,5,6 in the following DOI published by dryad. https://doi.org/10.5061/dryad.6q573n5z8
Article and author information
Author details
Funding
Austrian Science Fund (P 31599)
- Walter Sandtner
Austrian Science Fund (P 31813)
- Walter Sandtner
Austrian Science Fund (W1232)
- Harald H Sitte
Vienna Science and Technology Fund (CS15-033)
- Harald H Sitte
Vienna Science and Technology Fund (LS17-026)
- Michael Freissmuth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Bhat et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Handling of intracellular K+ determines voltage dependence of plasmalemmal monoamine transporter function
eLife 10:e67996.
https://doi.org/10.7554/eLife.67996
