Effects of midazolam on hERG K+ channel / 中国应用生理学杂志
Chinese Journal of Applied Physiology
; (6): 143-147, 2015.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-243397
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.</p><p><b>METHODS</b>Whole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.</p><p><b>RESULTS</b>Midazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.</p><p><b>CONCLUSION</b>Midazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Midazolam
/
Técnicas de Patch-Clamp
/
Bloqueadores dos Canais de Potássio
/
Relação Dose-Resposta a Droga
/
Canais de Potássio Éter-A-Go-Go
/
Células HEK293
/
Mutação
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Applied Physiology
Ano de publicação:
2015
Tipo de documento:
Artigo