Inhibition of K+ currents of outer hair cells in guinea pig cochlea by fluoxetine.
Eur J Pharmacol
; 453(2-3): 159-66, 2002 Oct 25.
Article
en En
| MEDLINE
| ID: mdl-12398899
ABSTRACT
The effects of fluoxetine (Prozac), a widely used antidepressant drug, on K+ channel in outer hair cells isolated from guinea pig cochlea were studied using the whole-cell patch clamp technique. Fluoxetine potently inhibited leak K+ currents with an IC50 of 0.78 microM. The inhibition was reversible and voltage-independent. At 45- to 103-fold higher concentrations than the plasma levels, fluoxetine reversibly blocked voltage-activated K+ currents. Kinetics of the current in the presence of fluoxetine resembled the control current, and the inhibition was not use-dependent. Neither the activation curve nor the reversal potential was affected by fluoxetine. This inhibition was voltage-dependent with an electric distance (delta value) of the binding site of at least 26% of the membrane field from the cytoplasmic side. Use-independent inhibition suggests that fluoxetine blocks the channel before its opening or instantly blocks the open channel. This is the first study of the action of this compound on K+ channel of outer hair cells of the mammalian inner ear. We conclude that the block of the leak K+ currents can occur at therapeutic levels of fluoxetine. Since the voltage-activated K+ currents are not potently blocked by fluoxetine, this action might not be related to its antidepressant action or adverse effects.
Buscar en Google
Bases de datos:
MEDLINE
Asunto principal:
Canales de Potasio
/
Fluoxetina
/
Inhibidores Selectivos de la Recaptación de Serotonina
/
Cóclea
/
Células Ciliadas Auditivas Externas
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos