Voltage dependence of monoamine transporter function is determined by handling of intracellular potassium

Abstract

The transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) tap the transmembrane Na+ gradient to fuel their concentrative power. It is, however, conceivable that these carrier proteins may also utilize other energy sources such as membrane voltage and/or the transmembrane K+ gradient. In order to delineate these forces, we investigated the role of intracellular cations and voltage on substrate transport through DAT, NET, and SERT. To this end, we simultaneously recorded substrate-induced currents and uptake of the fluorescent substrate APP+ (4-(4-dimethylamino)phenyl-1-methylpyridinium) into single HEK293 cells expressing either DAT, NET or SERT under voltage control.