Hydrocinnamic Acid Inhibits the Currents of WT and SQT3 Syndrome-Related Mutants of Kir2.1 Channel.
J Membr Biol
; 250(5): 425-432, 2017 Oct.
Article
en En
| MEDLINE
| ID: mdl-28660286
ABSTRACT
Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.1. Here, we determined a monomer, hydrocinnamic acid (HA), as the effective component from 18 compounds of styrax. Our data show that HA can inhibit the currents of Kir2.1 channel in both excised inside-out and whole-cell patch with the IC50 of 5.21 ± 1.02 and 10.08 ± 0.46 mM, respectively. The time course of HA blockage and washout are 2.3 ± 0.6 and 10.5 ± 2.6 s in the excised inside-out patch. Moreover, HA can also abolish the currents of D172N and E299V with the IC50 of 6.66 ± 0.57 and 5.81 ± 1.10 mM for D172N and E299V, respectively. Molecular docking results determine that HA binds with Kir2.1 at K182, K185, and K188, which are phosphatidylinositol 4,5-bisphosphate (PIP2) binding residues. Our results indicate that HA competes with PIP2 to bind with Kir2.1 and inhibits the currents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenilpropionatos
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Arritmias Cardíacas
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Canales de Potasio de Rectificación Interna
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Simulación del Acoplamiento Molecular
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Sistema de Conducción Cardíaco
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Cardiopatías Congénitas
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Potenciales de la Membrana
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Mutación
Límite:
Humans
Idioma:
En
Revista:
J Membr Biol
Año:
2017
Tipo del documento:
Article
País de afiliación:
China