Fluctuation analysis of norepinephrine and serotonin transporter currents

Findings from an electrophysiological analysis of neurotransmitter transporters show that transmitter-induced currents are associated with these transporters: For charged transmitters, such as NE and 5-HT, a fraction of the total current is carried by the transmitter itself; however, the transmitter also induces an extra current in analogy to an ligand-gated ion channel. An additional conductance not discussed in this article is the so-called leak, in which neurotransmitter transporters generate an ionic current in the absence of transmitter. Using a combination of flux measurements, voltage clamp, and fluctuation analysis has shown that, for norepinephrine and serotonin transporters, the transmitter-induced current greatly exceeds the transmitter current. Such data can provide an exact measure of the ratio of these charge movements to transmitter translocation at the molecular level, suggesting new strategies to understand neurotransmitter transporters.