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

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, for example, membrane voltage and/or the transmembrane K⁺ gradient. We have addressed 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 have shown 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.

SUBMITTER: Bhat S

PROVIDER: S-EPMC8192120 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Bhat Shreyas S Niello Marco M Schicker Klaus K Pifl Christian C Sitte Harald H HH Freissmuth Michael M Sandtner Walter W

eLife 20210601

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, for example, membrane voltage and/or the transmembrane K+ gradient. We have addressed this by recording uptake of endogenous substrates or the fluorescent substrate APP+(4-(4-dimethylamino)phenyl-1-methylpyridinium) under voltage cont ...[more]

PMID: 34061030

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

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Handling of intracellular K<sup>+</sup> determines voltage dependence of plasmalemmal monoamine transporter function.

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

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Handling of intracellular K&lt;sup&gt;+&lt;/sup&gt; determines voltage dependence of plasmalemmal monoamine transporter function.

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

Handling of intracellular K<sup>+</sup> determines voltage dependence of plasmalemmal monoamine transporter function.