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

Access this Article

Author(s)

    • 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

Abstract

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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 89(1), 53-63, 2002-05-01

    The Japanese Pharmacological Society

References:  41

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008431021
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    6169433
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top