Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells
The Korean Journal of Physiology and Pharmacology
;
: 75-82, 2017.
Article
in English
| WPRIM
| ID: wpr-728255
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Arrhythmias, Cardiac
/
Potassium
/
Tail
/
Long QT Syndrome
/
Potassium Channels
/
Patch-Clamp Techniques
/
Kidney
/
Acepromazine
Limits:
Humans
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2017
Type:
Article
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