DIRECT ROLE FOR POTASSIUM CHANNEL INHIBITION IN HYPOXIC PULMONARY VASOCONSTRICTION
DIRECT ROLE FOR POTASSIUM CHANNEL INHIBITION IN HYPOXIC PULMONARY VASOCONSTRICTION
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DOI：
10.1152/ajpcell.1992.262.4.c882
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发表时间：
1992-04-01
影响因子：
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通讯作者：
WEIR, EK
中科院分区：
文献类型：
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作者：
POST, JM;HUME, JR;WEIR, EK
在肺动脉细胞、离体灌注肺和肺动脉环中研究了导致缺氧肺血管收缩的细胞机制。三种 K+ 通道拮抗剂，五纹斑马蜂毒液、四乙铵和 4-氨基吡啶，通过增加肺动脉压力和张力来模拟离体肺和动脉环中缺氧的影响，并且还抑制离体肺动脉细胞中的全细胞 K+ 电流。将氧张力从常氧水平降低至低氧水平可直接抑制K+电流并导致分离的犬肺动脉平滑肌细胞膜去极化，但不会引起犬肾动脉平滑肌细胞膜去极化。尼索地平或用[1,2-双(2)氨基苯氧基]乙烷-N,N,N',N'-四乙酸对细胞内Ca2+浓度进行高缓冲可防止K+电流的缺氧抑制，表明Ca2+敏感的K+通道可能是缺氧反应的原因。这些结果表明 K+ 通道抑制可能是通过引起膜去极化和随后的 Ca2+ 进入而将缺氧与肺血管收缩联系起来的关键事件。
Cellular mechanisms responsible for hypoxic pulmonary vasoconstriction were investigated in pulmonary arterial cells, isolated perfused lung, and pulmonary artery rings. Three K+ channel antagonists, Leiurus quinquestriatus venom, tetraethylammonium, and 4-aminopyridine, mimicked the effects of hypoxia in isolated lung and arterial rings by increasing pulmonary artery pressure and tension and also inhibited whole cell K+ currents in isolated pulmonary arterial cells. Reduction of oxygen tension from normoxic to hypoxic levels directly inhibited K+ currents and caused membrane depolarization in isolated canine pulmonary arterial smooth muscle cells but not in canine renal arterial smooth muscle cells. Nisoldipine or high buffering of intracellular Ca2+ concentration with [1,2-bis(2)aminophenoxy] ethane-N,N,N',N'-tetraacetic acid prevented hypoxic inhibition of K+ current, suggesting that a Ca2+-sensitive K+ channel may be responsible for the hypoxic response. These results indicate that K+ channel inhibition may be a key event that links hypoxia to pulmonary vasoconstriction by causing membrane depolarization and subsequent Ca2+ entry.