Unifying concept of serotonin transporter-associated currents.
J Biol Chem
; 287(1): 438-445, 2012 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-22072712
ABSTRACT
Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Condutividade Elétrica
/
Proteínas da Membrana Plasmática de Transporte de Serotonina
/
Fenômenos Eletrofisiológicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article