GABA transporter lysine 448: a key residue for tricyclic antidepressants interaction.

The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (gamma-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially unaffected.

Transient currents in the glycine cotransporter GlyT1 reveal different steps in transport mechanism.

The relation between presteady-state (transient) currents elicited by voltage steps in the absence of organic substrate and transport-associated currents in the presence of glycine was investigated in Xenopus oocytes expressing the neuronal glycine transporter GlyT1b. Saturating amounts of glycine converted the transient currents in steady transport currents. Analysis of the transient currents abolished by the substrate confirmed the intramembrane nature of the underlying charge movement process.

Structural and functional basis of amino acid specificity in the invertebrate cotransporter KAAT1.

The substrate specificity of KAAT1, a Na+- and K+-dependent neutral amino acid cotransporter cloned from the larva of the invertebrate Manduca sexta and belonging to the SLC6A gene family has been investigated using electrophysiological and radiotracer methods. The specificity of KAAT1 was compared to that of CAATCH1, a strictly related transporter with different amino acid selectivity. Competition experiments between different substrates indicate that both transporters bind leucine more strongly than threonine and proline, the difference between KAAT1 and CAATCH1 residing in the incapacity of the latter to complete the transport cycle in presence of leucine.

Oligomeric structure of the neutral amino acid transporters KAAT1 and CAATCH1.

The highly homologous neutral amino acid transporters KAAT1 and CAATCH1, cloned from the midgut epithelium of the Manduca sexta larva, are members of the Na(+)/Cl(-)-dependent transporter family. Recent evidence indicates that transporters of this family form constitutive oligomers. CAATCH1 and KAAT1 give rise to specific kinds of current depending on the transported amino acid, cotransported ion, pH, and membrane voltage.