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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Does extracellular calcium determine what pool of GABA is the target for alpha-latrotoxin?
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Does extracellular calcium determine what pool of GABA is the target for alpha-latrotoxin?

机译：细胞外钙是否确定α-拉毒素的靶标是什么GABA库？

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摘要

Presynaptic neurotoxin alpha-latrotoxin, from the venom of Latrodectus mactans tredecimguttatus, causes massive [(3)H]GABA release from rat brain synaptosomes, irrespective of calcium presence in the extracellular medium. Whether the binding of alpha-latrotoxin to Ca(2+)-dependent (neurexin 1 alpha) or to Ca(2+)-independent (latrophilin) receptor triggers [(3)H]GABA release by the same mechanisms or different ones, inducing either exocytotic process or outflow by mobile membrane GABA transporter, is unknown. We examined alpha-latrotoxin-evoked [(3)H]GABA release from synaptosomes which cytosolic [(3)H]GABA pool was depleted either by applying competitive inhibitors of the GABA transporter, nipecotic acid and 2,4-diaminobutyric acid, or by permeation with digitonin. We also compared the effect of the GABA transporter inhibitors on depolarisation-evoked and alpha-latrotoxin-evoked [(3)H]GABA release using as depolarising agents 4-aminopyridine and high KCl in the Ca(2+)-containing and in Ca(2+)-free medium, respectively. Incubation of synaptosomes with nipecotic acid induced the essential acceleration of unstimulated [(3)H]GABA release and deep inhibition of high KCl-evoked Ca(2+)-independent [(3)H]GABA release. In contrast, at the similar conditions the effect of alpha-latrotoxin was greatly augmented with respect to the control response. Another way to assay what GABA pool was involved in alpha-latrotoxin-induced release lays in an analysis of the effects of depolarisation and alpha-latrotoxin in consecutive order. The preliminary 4-aminopyridine-stimulated [(3)H]GABA release attenuated the toxin effect. But when depolarisation occurred in Ca(2+)-free medium, no influence on alpha-latrotoxin effect was revealed. Employing digitonin-permeated synaptosomes, we have shown that alpha-latrotoxin could stimulate [3H]GABA release in the medium with 1mM EGTA, this effect of the toxin was blocked by concanavalin A and was ATP-dependent. The latter suggests that alpha-latrotoxin-released neurotransmitter has the vesicular nature. We assume that the type of the toxin membrane receptor does not determine the mechanisms of [(3)H]GABA release evoked by alpha-latrotoxin.
机译：突触前神经毒素α-lato毒素，来自Macros tredecimguttatus的毒液，导致大鼠脑突触小体大量释放[（3）H] GABA，与细胞外培养基中是否存在钙无关。无论是α-拉毒素与Ca（2+）依赖型（神经毒素1 alpha）或与Ca（2+）依赖型（latrophilin）受体结合，都是通过相同或不同的机制触发[（3）H] GABA释放的，通过移动膜GABA转运蛋白诱导胞吐过程或流出的机制尚不清楚。我们研究了通过应用GABA转运蛋白，乳糜酸和2,4-二氨基丁酸的竞争性抑制剂，耗尽了胞浆中[[3] H] GABA的突触小体释放的α-乳酸毒素引起的[（3）H] GABA释放。通过洋地黄皂苷的渗透。我们还比较了GABA转运蛋白抑制剂对去极化和α-拉托毒素诱发的[（3）H] GABA释放的影响，使用4-氨基吡啶和高KCl作为含Ca（2+）和Ca的去极化剂不含（2+）的培养基。突触小体与苯甲酸的温育诱导未刺激的[（3）H] GABA释放的本质加速和高KCl诱发的Ca（2+）独立[[3）H] GABA释放的深度抑制。相反，在类似条件下，就对照反应而言，α-拉毒素的作用大大增强。另一种测定什么GABA库参与α-拉托毒素诱导释放的另一种方法是按连续顺序分析去极化和α-拉托毒素的作用。初步的4-氨基吡啶刺激的[（3）H] GABA释放减弱了毒素的作用。但是，当去极化发生在无Ca（2+）的培养基中时，没有发现对α-拉毒素的影响。使用洋地黄皂苷渗透的突触小体，我们已经证明α-拉毒素可以刺激含1mM EGTA的培养基中的[3H] GABA释放，这种毒素的作用被伴刀豆球蛋白A阻断，并且是ATP依赖性的。后者表明α-乳酸毒素释放的神经递质具有水泡性质。我们假定毒素膜受体的类型不能确定由α-拉托毒素引起的[（3）H] GABA释放的机制。

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