Blockade of voltage-gated K+ currents in rat mesenteric arterial smooth muscle cells by MK801

Journal of Pharmacological Sciences

Jae Gon Kim¹  Hana Cho¹  Dong Jun Sung²  Bokyung Kim³  Sang Woong Park³  Hai Yue Lin³  Kyung Chul Shin³  Jeong Min Kim³  Young Min Bae³ 

[1] Department of Physiology and the Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea;Division of Sport Science, College of Science and Technology, Konkuk University, Chungju, 380-701, South Korea;KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea;

关键词: MK801;    Voltage-gated K+ channels;    Phencyclidine;    Schizophrenia;    Hypertension;   

DOI  :  10.1016/j.jphs.2014.11.005

来源: DOAJ

【 摘 要 】

MK801 (dizocilpine), a phencyclidine (PCP) derivative, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). Another PCP derivative, ketamine, was reported to block voltage-gated K+ (Kv) channels, which was independent of NMDAr function. Kv currents are major regulators of the membrane potential (Em) and excitability of muscles and neurons. Here, we investigated the effect of MK801 on the Kv channels and Em in rat mesenteric arterial smooth muscle cells (RMASMCs). We used the whole-cell patch clamp technique to analyze the effect of MK801 enantiomers on Kv channels and Em. (+)MK801 inhibited Kv channels in a concentration-dependent manner (IC50 of 89.1 ± 13.1 μM, Hill coefficient of 1.05 ± 0.08). The inhibition was voltage- and state- independent. (+)MK801 didn't influence steady-state activation and inactivation of Kv channels. (+)MK801 treatment depolarized Em in a concentration-dependent manner and concomitantly decreased membrane conductance. (−)MK801 also similarly inhibited the Kv channels (IC50 of 134.0 ± 17.5 μM, Hill coefficient of 0.87 ± 0.09). These results indicate that MK801 directly inhibits the Kv channel in a state-independent manner in RMASMCs. This MK801-mediated inhibition of Kv channels should be considered when assessing the various pharmacological effects produced by MK801, such as schizophrenia, neuroprotection, and hypertension.

【 授权许可】

Unknown