Inhibition of Kir4.1 potassium channels by quinacrine.
Brain Res
; 1663: 87-94, 2017 05 15.
Article
em En
| MEDLINE
| ID: mdl-28288868
Inwardly rectifying potassium (Kir) channels are expressed in many cell types and contribute to a wide range of physiological processes. Particularly, Kir4.1 channels are involved in the astroglial spatial potassium buffering. In this work, we examined the effects of the cationic amphiphilic drug quinacrine on Kir4.1 channels heterologously expressed in HEK293 cells, employing the patch clamp technique. Quinacrine inhibited the currents of Kir4.1 channels in a concentration and voltage dependent manner. In inside-out patches, quinacrine inhibited Kir4.1 channels with an IC50 value of 1.8±0.3µM and with extremely slow blocking and unblocking kinetics. Molecular modeling combined with mutagenesis studies suggested that quinacrine blocks Kir4.1 by plugging the central cavity of the channels, stabilized by the residues E158 and T128. Overall, this study shows that quinacrine blocks Kir4.1 channels, which would be expected to impact the potassium transport in several tissues.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinacrina
/
Canais de Potássio Corretores do Fluxo de Internalização
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Holanda