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代谢抑制剂对体外灌流的海马脑片诱发活性及能量状态的影响。

Effects of metabolic inhibitors on evoked activity and the energy state of hippocampal slices superfused in vitro.

作者信息

Cox D W, Drower J, Bachelard H S

出版信息

Exp Brain Res. 1985;57(3):464-70. doi: 10.1007/BF00237833.

DOI:10.1007/BF00237833
PMID:2984037
Abstract

The effects of the metabolic inhibitors, arsenate (1,10 mM), iodoacetate (1 mM), alpha-cyano-4-hydroxycinnamate (alpha C4HC: 0.05, 0.15, 0.5 mM), malonate (10 mM) and 2,4-dinitrophenol (10 microM) on granule cell evoked activity and levels of energy metabolites of superfused hippocampal slices were investigated. Every inhibitor tested decreased the amplitudes of the population spikes, and also to a lesser extent, the rates of rise of EPSP. The effects were essentially reversible except in the case of iodoacetate. Concentrations of inhibitors, sufficient to depress evoked activity by at least 75%, did not significantly decrease tissue levels of phosphocreatine, ATP or total K+, with the exception of 1 mM iodoacetate. In slices superfused with 10 mM arsenate, 0.5 mM alpha C4HC, 10 mM malonate or 10 micron 2,4-dinitrophenol, the threshold EPSP for population spike generation was significantly higher than in inhibitor-free medium. These results are discussed in relation to the potential importance of non-oxidative glucose metabolism in maintaining evoked activity, and the possibility that during metabolic insults, tissue ATP utilisation is decreased to match reduced cytoplasmic ATP supply.

摘要

研究了代谢抑制剂砷酸盐(1、10 mM)、碘乙酸盐(1 mM)、α-氰基-4-羟基肉桂酸(αC4HC:0.05、0.15、0.5 mM)、丙二酸盐(10 mM)和2,4-二硝基苯酚(10 μM)对灌流海马切片颗粒细胞诱发活性和能量代谢物水平的影响。所测试的每种抑制剂均降低了群体峰电位的幅度,并且在较小程度上也降低了兴奋性突触后电位(EPSP)的上升速率。除碘乙酸盐外,这些影响基本上是可逆的。足以使诱发活性至少降低75%的抑制剂浓度,除了1 mM碘乙酸盐外,并未显著降低磷酸肌酸、三磷酸腺苷(ATP)或总钾离子的组织水平。在用10 mM砷酸盐、0.5 mM αC4HC、10 mM丙二酸盐或10 μM 2,4-二硝基苯酚灌流的切片中,群体峰电位产生的阈下EPSP显著高于无抑制剂的培养基。结合非氧化葡萄糖代谢在维持诱发活性中的潜在重要性,以及在代谢损伤期间组织ATP利用减少以匹配细胞质ATP供应减少的可能性,对这些结果进行了讨论。

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