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KMID : 0811720170210010075
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Korean Journal of Physiology & Pharmacology
2017 Volume.21 No. 1 p.75 ~ p.82
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Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells
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Joo Young-Shin
Lee Hong-Joon
Choi Jin-Sung
Sung Ki-Wug
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Abstract
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The effects of acepromazine on human ether-a-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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KEYWORD
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Acepromazine, hERG currents, Long QT syndrome, Patch-clamp technique, Potassium channel
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