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A target K+ channel for the LP-805-induced hyperpolarization in smooth muscle cells of the rabbit portal vein

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Summary

The resting membrane potential of smooth muscle cells of the rabbit portal vein was −51.2 mV. LP-805 (8-tert-butyl-6,7-dihydropyrrolo[3,2-e] 5-methylpyrazolo [1,5-a] pyrimidine-3-carbonitrile) hyperpolarized the membrane to −62.3 mV (10 μM) and inhibited the burst spike discharges as measured using the microelectrode method. In dispersed smooth muscle cells, LP-805 (10 μM) generated an outward-current with a maximum amplitude of 68 pA at a holding potential of −40 mV in experiments using the voltage-clamp procedure. The reversal potential of the outward current evoked by LP-805 was −82 mV and this value was close to the equilibrium potential for K+ (−80 mV) in the present ionic conditions, suggesting that LP-805 activated the K+ channel. Generation of both the hyperpolarization and the outward c urrent by LP-805 was inhibited by glibenclamide (≥ 1 μM). Using the cell-attached and cell-free patch-clamp (in the presence of GDP) procedures, the maxi-K+ channel current (150 pS) could be recorded in the absence of LP-805; application of LP-805 additionally opened a small conductance K+ channel current (15 pS) without change in the activity of the maxi-K+ channel. The maxi-K+ channel was sensitive to charybdotoxin (0.1 μM) and to intracellular Ca2+ ([Ca2+]i) concentration. The 15 pS channel was insensitive to [Ca2+]i and charybdotoxin, but sensitive to intracellular ATP concentration. Glibenclamide (> 1 μM) inhibited the 15 pS K+ channel activated by LP-805. These actions of LP-805 on the maxi-K+ and 15 pS K+ channels are the same as those previously observed for nicorandil and pinacidil. Thus, LP-805 is a K+ channel opener with a chemical structure different from those of the known openers.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Kyushu University, 812, Fukuoka, Japan

    Masahiro Kamouchi, Shunichi Kajioka, Takeshi Sakai, Kenji Kitamura & Hirosi Kuriyama

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  1. Masahiro Kamouchi
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  2. Shunichi Kajioka
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  3. Takeshi Sakai
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  4. Kenji Kitamura
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  5. Hirosi Kuriyama
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Correspondence to M. Kamouchi at the above address

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Kamouchi, M., Kajioka, S., Sakai, T. et al. A target K+ channel for the LP-805-induced hyperpolarization in smooth muscle cells of the rabbit portal vein. Naunyn-Schmiedeberg's Arch Pharmacol 347, 329–335 (1993). https://doi.org/10.1007/BF00167453

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  • DOI: https://doi.org/10.1007/BF00167453

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