Mechanisms Underlying the Activation of Large Conductance CA^<2+>-Activated K^+ Channels by Nordihydroguaiaretic Acid

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著者

    • MURAKI Katsuhiko
    • Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University
    • IMAIZUMI Yuji
    • Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University

抄録

The mechanisms underlying the activation of large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK) channel by nordihydroguaiaretic acid (NDGA) were examined in human embryonic kidney (HEK293) cells, where BK channel α (BKα) or α plus β1 subunit (BKαβ1) was heterologously expressed, and also in freshly isolated porcine coronary arterial smooth muscle cells (PCASMCs). The activity of both BKα and BK αβ1 channels was increased by 10 μM NDGA in similar manners, indicating the selective action on the α subunit to increase Ca<sup>2+</sup> sensitivity. The application of NDGA to PCASMCs induced outward current and hyperpolarization under voltage and current clamp, respectively, in a concentration-dependent manner (≥3 μM). These effects were blocked by 100 nM iberiotoxin. Electrical events induced by NDGA (≥10 μM) were, unexpectedly, associated with the increase in [Ca<sup>2+</sup>]<sub>i</sub>. After the treatment with caffeine and ryanodine, the [Ca<sup>2+</sup>]<sub>i</sub> increase by NDGA was markedly reduced and the hyperpolarization by NDGA was attenuated. The Ca<sup>2+</sup> release by 10 μM NDGA was preceded by membrane depolarization of mitochondria. These results indicate that BK channel opening by NDGA in PCASMCs is due to the direct action on α subunit and also to Ca<sup>2+</sup> release from sarcoplasmic reticulum, presumably via, at least in part, the inhibition of mitochondria respiration.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 89(1), 53-63, 2002-05-01

    The Japanese Pharmacological Society

参考文献:  41件中 1-41件 を表示

被引用文献:  2件中 1-2件 を表示

各種コード

  • NII論文ID(NAID)
    10008431021
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    6169433
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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