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.
Li
Ming
M
Division of Biology 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Farley
Robert A
RA
Lester
Henry A
HA
D000818:Animals; D002021:Buffers; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D006531:HEPES / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels; D008024:Ligands; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013997:Time Factors; D014982:Xenopus laevis
D002021:Buffers; D002352:Carrier Proteins; D007473:Ion Channels; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D013096:Spermine; D012701:Serotonin; D006531:HEPES; D013095:Spermidine