Inhibitory effects of SKF96365 on the activities of K<sup>+</sup> channels in mouse small intestinal smooth muscle cells

  • TANAHASHI Yasuyuki
    Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603–8555, Japan
  • WANG Ban
    Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603–8555, Japan
  • MURAKAMI Yuri
    Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-Ku, Kyoto 603–8555, Japan
  • UNNO Toshihiro
    Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan
  • MATSUYAMA Hayato
    Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan
  • NAGANO Hiroshi
    Department of Pathogenetic Veterinary Science, United Graduate School of Veterinary Science, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan
  • KOMORI Seiichi
    Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1–1 Yanagido, Gifu 501–1193, Japan

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  • Inhibitory effects of SKF96365 on the activities of K⁺ channels in mouse small intestinal smooth muscle cells

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Abstract

In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K+ channel currents, we recorded currents through ATP sensitive K+ (IKATP), voltage-gated K+ (IKv) and Ca2+ activated K+ channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), which is a selective ATP sensitive K+ channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from −80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. These results indicated that SKF inhibited ATP sensitive K+ channels and voltage-gated K+ channels, with the ATP sensitive K+ channels being more sensitive than the voltage-gated K+ channels. These inhibitory effects on K+ channels should be considered when SKF is used as a cationic channel blocker.

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