Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

• Tanaka Hikaru

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Takahashi Yukiko

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Hamaguchi Shogo

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Iida-Tanaka Naoko

  Department of Food Science, Otsuma Women’s University

• Oka Takayuki

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Nishio Masato

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Ohtsuki Atsushi

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

• Namekata Iyuki

  Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences

抄録

The effects of terfenadine and pentamidine on the human ether-a-go-go related gene (hERG) channel current and its intracellular trafficking were evaluated. Green fluorescent protein (GFP)-linked hERG channels were expressed in HEK293 cells, and the membrane current was measured by an automated whole cell voltage clamp system. To evaluate drug effects on channel trafficking to the cell membrane, the fraction of channel present on the cell membrane was quantified by current measurement after drug washout and confocal microscopy. Terfenadine directly blocked the hERG channel current but had no effect on trafficking of hERG channels to the cell membrane after application in culture medium for 2 d. In contrast, pentamidine had no direct effect on the hERG channel current but reduced trafficking of hERG channels. The two drugs inhibited hERG channel function through different mechanisms: terfenadine through direct channel blockade and pentamidine through inhibition of channel trafficking to the cell membrane. Combined use of automated voltage clamp and confocal microscopic analyses would provide insights into the mechanisms of drug-induced QT-prolongation and arrhythmogenesis.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 37 (11), 1826-1830, 2014

  公益社団法人 日本薬学会

キーワード

• human ether-a-go-go related gene (hERG)
• intracellular trafficking
• arrhythmia
• terfenadine
• pentamidine

詳細情報

• CRID: 1390001204633789696
• NII論文ID: 130004703898
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00417
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 025880593
• PubMed: 25366487
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025880593
• Web Site: https://www.jstage.jst.go.jp/article/bpb/37/11/37_b14-00417/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015248466
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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