Na+ pump inhibition and non‐selective cation channel activation by cyanide and anoxia in guinea‐pig chromaffin cells

Na+ pump inhibition and non‐selective cation channel activation by cyanide and anoxia in guinea‐pig chromaffin cells
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氰化物和缺氧对豚鼠嗜铬细胞中 Na+ 泵的抑制和非选择性阳离子通道激活

DOI:
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发表时间:
1999
期刊:
Journal of Physiology
影响因子:
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通讯作者:
I. Imanaga
I. Imanaga
中科院分区:
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文献类型:
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作者:
Masumi Inoue;N. Fujishiro;I. Imanaga

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1缺氧和氰化物(CN)代谢抑制通过去极化引起肾上腺嗜铬细胞分泌儿茶酚胺。我们使用穿孔贴片方法阐明了CN或缺氧诱导的内向(去极化)电流的机制。Ba 2+的2浴应用诱导了毒蕈碱诱导电流(伊穆斯)和部分CN诱导电流(ICN)的剂量依赖性抑制,IC 50(50%抑制浓度)为1.3 mM。估计Ba 2+敏感组分占总ICN的58%。3 ICN的Ba 2+抗性成分倾向于随着膜电位从-40 mV移动到40 mV而增加,并且通过暴露于无K+溶液或200 μm哇巴因而受到显著抑制,表明ICN的大部分Ba 2+抗性成分是由于Na+泵电流(Ipump)的抑制。ICN的非Ipump组分在无K+溶液中逐渐减少。在无K+ CN溶液中用葡萄糖取代蔗糖进一步降低了CN产生非Ipump组分的效力。5 ICN的非Ipump组分的I-V关系在147和5.5 mM Na+下分别具有-3和-47 mV的逆转电位,并显示出向外整流,表明ICN的非Ipump组分是由于非选择性阳离子通道的激活。6缺氧诱导的电流幅度与ICN相当,缺氧诱导的电流明显阻断了ICN的发育。在不存在K+的情况下,缺氧诱导的电流减少约60%,并且在无K+条件下在5 mV时极性反转。5可以得出结论,暴露于CN和缺氧诱导Na+泵的抑制和非选择性阳离子通道的激活,这可能是由于主要由Na+泵消耗引起的ATP减少。
1 Hypoxia and metabolic inhibition with cyanide (CN) evoke catecholamine secretion in adrenal chromaffin cells through depolarization. We elucidated mechanisms for a CN‐ or anoxia‐induced inward (depolarization) current, using the perforated patch method. 2 Bath application of Ba2+ induced a dose‐dependent inhibition of a muscarine‐induced current (IMUS) and part of the CN‐induced current (ICN) with an IC50 (concentration responsible for 50 % inhibition) of 1.3 mM. The Ba2+‐sensitive component was estimated to comprise 58 % of the total ICN. 3 The Ba2+‐resistant component of ICN tended to increase with shifts of membrane potential from ‐40 to 40 mV and was markedly suppressed by exposure to a K+‐free solution or 200 μm ouabain, indicating that the majority of the Ba2+‐resistant component of ICN is due to suppression of the Na+ pump current (Ipump). 4 The non‐Ipump component of ICN diminished progressively in K+‐free solution. Substitution of glucose for sucrose in a K+‐free CN solution further diminished the CN potency to produce the non‐Ipump component. 5 The I‐V relationship for the non‐Ipump component of ICN had a reversal potential of ‐3 and ‐47 mV at 147 and 5.5 mM Na+, respectively, and showed an outward rectification, indicating that the non‐Ipump component of ICN is due to activation of non‐selective cation channels. 6 Exposure to anoxia induced a current with an amplitude comparable to that of ICN, and the anoxia‐induced current apparently occluded development of ICN. The anoxia‐induced current diminished by ca 60 % in the absence of K+ and reversed polarity at 5 mV under K+‐free conditions. 5 It is concluded that exposure to CN and to anoxia induces suppression of the Na+ pump and activation of non‐selective cation channels, probably due to an ATP decrease resulting mainly from consumption by the Na+ pump.
DOI: 10.1161/01.res.73.6.1100
发表时间: 1993-12-01
影响因子: 20.1
作者:
ARCHER, SL;HUANG, J;WEIR, EK
通讯作者: WEIR, EK