Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices

Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices
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DOI:
10.1016/s0006-8993(99)01674-1
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发表时间:
1999-08-14
期刊:
影响因子:
2.9
通讯作者:
Aitken, P
Aitken, P
中科院分区:
医学3区
文献类型:
--
作者:
Balestrino, M;Young, J;Aitken, P

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我们用瓦苦因(100 μ M)阻断离体大鼠海马片Na+,K+ atp酶。这种治疗足以引起突然去极化,这是扩散性抑郁症(SD)和类似SD的缺氧去极化(AD)的标志。这种去极化伴随着[K](o)的急剧增加,也让人联想到SD和AD期间观察到的情况。瓦巴因诱导的SD不需要Na+, K+ atp酶的完全失活,因为它发生时酶仍然能够提供V-o和[K](o)的恢复。数据表明,Na+,K+ atp酶本身的功能失活会引发导致sd样AD的事件。这种瓦巴因诱导的去极化不受突触传递阻滞的影响,而是被细胞外空间的高渗透压所消除。讨论了这些发现与AB病理生理的可能相关性。(C) 1999 Elsevier Science B.V.版权所有
We used ouabain (100 mu M) to block Na+,K+ ATPase of in vitro rat hippocampal slices. This treatment was sufficient to cause the sudden depolarization that is the hallmark of both spreading depression (SD) and of the SD-like anoxic depolarization (AD). This depolarization was accompanied by a large and sudden increase in [K](o), also reminiscent of that observed during both SD and AD. Ouabain-induced SD did not require a complete inactivation of Na+, K+ ATPase, as it occurred when the enzyme was still capable of providing recovery of both V-o and [K](o). The data indicate that functional inactivation of Na+,K+ ATPase per se initiates events that lead to an SD-like AD. This ouabain-induced depolarization was not affected by block of synaptic transmission, instead it was abolished by hyperosmolarity of the extracellular space. The possible relevance of these findings to the pathophysiology of AB is discussed. (C) 1999 Elsevier Science B.V. All rights reserved.