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Blockade of the human ether-a-go-go-related gene potassium channel by ketamine.
J Pharm Pharmacol. 2013 Sep; 65(9):1321-8.JP

Abstract

OBJECTIVES

The inhibition of the cardiac rapid delayed rectifier potassium current (IKr) and its cloned equivalent human ether-a-go-go-related gene (hERG) channel illustrate QT interval prolonging effects of a wide range of clinically used drugs. In this study, the direct interaction of the intravenous anaesthetic ketamine with wild-type (WT) and mutation hERG currents (IhERG) was investigated.

METHODS

The hERG channel (WT, Y652A and F656A) was expressed in Xenopus oocytes and studied using standard two-microelectrode voltage-clamp techniques.

KEY FINDINGS

WT hERG is blocked in a concentration-dependent manner with IC50 = 12.05 ± 1.38 μm by ketamine, and the steady-state inactivation curves are shifted to more negative potentials (about -27 mV). The mutation to Ala of Y652 and F656 located on the S6 domain attenuate IhERG blockade by ketamine, and produced approximately 9-fold and 2.5-fold increases in IC50 compared with that of WT hERG channel, respectively.

CONCLUSIONS

Ketamine blocks WT IhERG expressed in Xenopus oocytes in a concentration-dependent manner and predominantly interacts with the open hERG channels. The interaction of ketamine with hERG channel may involve the aromatic residues Tyr652 and Phe656.

Authors+Show Affiliations

Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23927470

Citation

Zhang, Peihua, et al. "Blockade of the Human Ether-a-go-go-related Gene Potassium Channel By Ketamine." The Journal of Pharmacy and Pharmacology, vol. 65, no. 9, 2013, pp. 1321-8.
Zhang P, Xing J, Luo A, et al. Blockade of the human ether-a-go-go-related gene potassium channel by ketamine. J Pharm Pharmacol. 2013;65(9):1321-8.
Zhang, P., Xing, J., Luo, A., Feng, J., Liu, Z., Gao, C., & Ma, J. (2013). Blockade of the human ether-a-go-go-related gene potassium channel by ketamine. The Journal of Pharmacy and Pharmacology, 65(9), 1321-8. https://doi.org/10.1111/jphp.12095
Zhang P, et al. Blockade of the Human Ether-a-go-go-related Gene Potassium Channel By Ketamine. J Pharm Pharmacol. 2013;65(9):1321-8. PubMed PMID: 23927470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of the human ether-a-go-go-related gene potassium channel by ketamine. AU - Zhang,Peihua, AU - Xing,Junlian, AU - Luo,Antao, AU - Feng,Juan, AU - Liu,Zhipei, AU - Gao,Chenghao, AU - Ma,Jihua, Y1 - 2013/07/10/ PY - 2013/01/13/received PY - 2013/05/12/accepted PY - 2013/8/10/entrez PY - 2013/8/10/pubmed PY - 2014/2/26/medline KW - human ether-a-go-go-related gene KW - ketamine KW - potassium channels KW - voltage clamp techniques SP - 1321 EP - 8 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 65 IS - 9 N2 - OBJECTIVES: The inhibition of the cardiac rapid delayed rectifier potassium current (IKr) and its cloned equivalent human ether-a-go-go-related gene (hERG) channel illustrate QT interval prolonging effects of a wide range of clinically used drugs. In this study, the direct interaction of the intravenous anaesthetic ketamine with wild-type (WT) and mutation hERG currents (IhERG) was investigated. METHODS: The hERG channel (WT, Y652A and F656A) was expressed in Xenopus oocytes and studied using standard two-microelectrode voltage-clamp techniques. KEY FINDINGS: WT hERG is blocked in a concentration-dependent manner with IC50 = 12.05 ± 1.38 μm by ketamine, and the steady-state inactivation curves are shifted to more negative potentials (about -27 mV). The mutation to Ala of Y652 and F656 located on the S6 domain attenuate IhERG blockade by ketamine, and produced approximately 9-fold and 2.5-fold increases in IC50 compared with that of WT hERG channel, respectively. CONCLUSIONS: Ketamine blocks WT IhERG expressed in Xenopus oocytes in a concentration-dependent manner and predominantly interacts with the open hERG channels. The interaction of ketamine with hERG channel may involve the aromatic residues Tyr652 and Phe656. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/23927470/Blockade_of_the_human_ether_a_go_go_related_gene_potassium_channel_by_ketamine_ L2 - https://doi.org/10.1111/jphp.12095 DB - PRIME DP - Unbound Medicine ER -