title: Blockade of voltage-gated K⁺ currents in rat mesenteric arterial smooth muscle cells by MK801.
abstract: 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.
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea.
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Park
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea.
authors.forename: Hai Yue
authors.initials: HY
authors.lastname: Lin
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Shin
authors.affiliation: Division of Sport Science, College of Science and Technology, Konkuk University, Chungju, 380-701, South Korea.
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Sung
authors.affiliation: Department of Physiology and the Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Jae Gon
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Physiology and the Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: KU Open Innovation Center, Research Institute of Medical Science, Chungju, Chungbuk, 380-701, South Korea; Department of Physiology, Konkuk University School of Medicine, Chungju, Chungbuk, 380-701, South Korea. Electronic address: ymbae30@kku.ac.kr.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Bae
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D013237:Stereoisomerism
chemical_list: D024642:Potassium Channels, Voltage-Gated; D016291:Dizocilpine Maleate
keywords: Hypertension; MK801; Phencyclidine; Schizophrenia; Voltage-gated K(+) channels