Highlighted Paper selected by Editor-in-Chief : Blockade of HERG Human K⁺ Channels by the Antidepressant Drug Paroxetine
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- Lee Seung Ho
- Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School
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- Sung Min Ji
- Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School
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- Lee Hyang Mi
- Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School
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- Chu Daehyun
- Department of Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine
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- Hahn Sang June
- Department of Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine
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- Jo Su-Hyun
- Department of Physiology, Institute of Bioscience and Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine
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- Choe Han
- Department of Physiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine
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- Choi Bok Hee
- Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School
書誌事項
- タイトル別名
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- Blockade of HERG Human K<sup>+</sup> Channels by the Antidepressant Drug Paroxetine
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The effects of paroxetine, a selective serotonin reuptake inhibitor, on human ether-a-go-go-related gene (HERG) channels were investigated using the whole-cell patch-clamp technique. The HERG channels were stably expressed in human embryonic kidney cells. Paroxetine inhibited the peak tail currents of the HERG channel in a concentration-dependent manner, with an IC50 value of 0.45 µM and a Hill coefficient of 0.85. These effects were reversible after wash-out of the drug. The paroxetine-induced inhibition of the HERG channels was voltage-dependent. There was a steep increase in inhibition over the voltage range of the channel opening. Also, a shallow voltage-dependent inhibition was detected over the voltage range in which the channels were fully activated. The fractional electrical distance was estimated to be 0.11. Paroxetine induced a leftward shift in the voltage-dependence of the steady-state activation of the HERG channels. Before and after application of the 1 µM paroxetine, the half-maximum activation was −14.21 mV and −27.04 mV, respectively, with no shift in the slope value. The HERG channel block was not use-dependent. The characteristics of the block were dependent on open and inactivated channel states rather than closed state. Paroxetine had no effect on activation and deactivation kinetics, steady-state inactivation. These results suggest that paroxetine blocks the HERG channels by binding to these channels in the open and inactivated states.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (9), 1495-1504, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633731968
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- NII論文ID
- 130004684791
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2M%2FmvFKhuw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025736936
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- PubMed
- 25177033
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可