Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells.
10.4196/kjpp.2017.21.1.75
- Author:
Young Shin JOO
1
;
Hong Joon LEE
;
Jin Sung CHOI
;
Ki Wug SUNG
Author Information
1. Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. sungkw@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Acepromazine;
hERG currents;
Long QT syndrome;
Patch-clamp technique;
Potassium channel
- MeSH:
Acepromazine*;
Arrhythmias, Cardiac;
Humans*;
Kidney*;
Long QT Syndrome;
Patch-Clamp Techniques;
Potassium Channels*;
Potassium*;
Tail
- From:The Korean Journal of Physiology and Pharmacology
2017;21(1):75-82
- CountryRepublic of Korea
- Language:English
-
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.
