Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells
The Korean Journal of Physiology and Pharmacology
; : 75-82, 2017.
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| ID: wpr-728255
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WPRO
ABSTRACT
The effects of acepromazine on human ether-à-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an IC₅₀ value of 1.5 µM and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between –40 and +10 mV. Before and after application of acepromazine, the half activation potentials of hERG currents changed to hyperpolarizing direction. Acepromazine blocked both the steady-state hERG currents by depolarizing pulse and the peak tail currents by repolarizing pulse; however, the extent of blocking by acepromazine in the repolarizing pulse was more profound than that in the depolarizing pulse, indicating that acepromazine has a high affinity for the open state of the channels, with a relatively lower affinity for the closed state of hERG channels. A fast application of acepromazine during the tail currents inhibited the open state of hERG channels in a concentration-dependent. The steady-state inactivation of hERG currents shifted to the hyperpolarized direction by acepromazine. These results suggest that acepromazine inhibits the hERG channels probably by an open- and inactivated-channel blocking mechanism. Regarding to the fact that the hERG channels are the potential target of drug-induced long QT syndrome, our results suggest that acepromazine can possibly induce a cardiac arrhythmia through the inhibition of hERG channels.
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Assunto principal:
Arritmias Cardíacas
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Potássio
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Cauda
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Síndrome do QT Longo
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Canais de Potássio
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Técnicas de Patch-Clamp
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Rim
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Acepromazina
Limite:
Humans
Idioma:
En
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2017
Tipo de documento:
Article