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    Please use this identifier to cite or link to this item: https://ir.fy.edu.tw:8080/ir/handle/987654321/2154

    Title: Activation of Large Conductance Ca2+-activated K+ Channels by Pinacidil in Human Umbilical Vascular Endothelial Cells.
    Authors: Sheng-Nan Wu;Hui-Fang Li;Ai-Yu Shen
    Contributors: 輔英科技大學 物理治療系
    Keywords: Pinacidil;Potassium channel antagonist;Antihypertensive agent;Activation;Endothelial cell;Umbilical vein;Blood vessel;Circulatory system;Human;Ionic channel;Calcium Cations;Potassium Cations;In vitro;Electrophysiology;Ionic current;Guanidines
    Date: 1999-02-01
    Issue Date: 2010-09-26 12:13:54 (UTC+8)
    Abstract: The effect of pinacidil, an opener of ATP-sensitive K+ (KATP) channels, on large-conductance Ca2+-activated K+ (BKCa) channels was investigated in cultured endothelial cells of human umbilical veins. In whole cell configuration, pinacidil (30 μM) increased the amplitude of K+ outward currents (Iκ). Charybdotoxin (100 nM), but not glibenclamide (10 μM), suppressed pinacidil-induced increase in Iκ. Neither carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 10 μM), an inhibitor of mitochondrial Ca2+-uniporter, nor cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore, affected pinacidil-induced increase in Iκ. In inside-out patch configuration, bath application of pinacidil (30 μM) did not change single channel conductance but increased the activity of BKCa channels. Pinacidil (30 μM) shifted the activation curve of BKCa channels to less positive membrane potential by approximately 15 mV. Pinacidil stimulated the activity of these channels in a concentration-dependent manner. The EC50 value for pinacidil-induced channel activity was 20 μM. After BKCa channels had been enhanced by Evans blue (100 μM), subsequent application of pinacidil (100 μM) did not further increase the channel activity. These results clearly indicate that in addition to the activation of KATP channels, pinacidil can also stimulate BKCa channels in endothelial cells. These effects could contribute to the regulation of vascular tone if similar results were found in endothelial cells in vivo.
    Relation: Drug Dev. Res. 48,6-16
    Appears in Collections:[物理治療系] 期刊論文

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