Voltage-dependent transient currents of human and rat 5-HT transporters (SERT) are blocked by HEPES and ion channel ligands

The hyperpolarization-activated transient current of mammalian 5-hydroxytryptamine transporters (SERT) expressed in Xenopus oocytes was studied. Human (h) and rat (r) SERT transient currents are blocked by HEPES with changes in the waveform kinetics, and the blockade of hSERT has use-dependent properties. HEPES also changes the time course of the prepriming step, especially for hSERT. Transient currents at hSERT and rSERT are also blocked by spermine and spermidine in the mM range, and by fluoxetine, cocaine, QX-314, and QX-222 in the microM range. These pharmacological and kinetic properties of transient current blockade emphasize the similarities between the transient current and phenomena at ion channels.