Details

Autor(en) / Beteiligte

• Zhang, Peihua
• Xing, Junlian
• Luo, Antao
• Feng, Juan
• Liu, Zhipei
• Gao, Chenghao
• Ma, Jihua

Titel

Blockade of the human ether-a-go-go-related gene potassium channel by ketamine

Ist Teil von

• Journal of pharmacy and pharmacology, 2013-09, Vol.65 (9), p.1321-1328

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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.