Role of taurine uptake on the induction of long-term synaptic potentiation
Role of taurine uptake on the induction of long-term synaptic potentiation
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DOI：
10.1111/j.1460-9568.2004.03309.x
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发表时间：
2004-04-01
影响因子：
3.4
通讯作者：
Solís, JM
中科院分区：
文献类型：
--
作者：
del Olmo, N;Suárez, LM;Solís, JM
牛磺酸应用于大鼠海马CA1区可诱导兴奋性突触传递的长时程增强，其机制与长时程增强（L-LTP）的后期有一定的相似性。先前的间接证据，如温度和钠依赖表明牛磺酸摄取是导致牛磺酸诱导的突触增强的主要步骤之一。我们发现牛磺酸诱导的增强与细胞内牛磺酸的积累无关，也不会被2-胍基乙磺酸（牛磺酸转运抑制剂，牛磺酸转运蛋白的底物）损害。我们发现海马突触体中的牛磺酸摄取被SKF 89976A抑制，SKF 89976A是一种GABA摄取阻断剂，不能被GABA转运体转运。SKF 89976A防止牛磺酸应用诱导突触增强。这种作用既不能被尼泊替酸模仿，尼泊替酸是一种广泛的GABA转运蛋白抑制剂，不影响牛磺酸的摄取，也不能被NO-711模仿，这是一种特异性和有效的GABA转运蛋白GAT-1抑制剂。此外，高频刺激序列诱导的L-LTP也被SKF 89976A抑制，而牛磺酸在不改变基础突触传递的浓度下克服了这种抑制。我们得出结论，牛磺酸通过激活运输牛磺酸的系统诱导突触增强，牛磺酸摄取是诱导突触可塑性现象（如L-LTP）所必需的。
Taurine application in the CA1 area of rat hippocampal slices induces a long-lasting potentiation of excitatory synaptic transmission that has some mechanistic similitude with the late phase of long-term potentiation (L-LTP). Previous indirect evidence such as temperature and sodium dependence indicated that taurine uptake is one of the primary steps leading to the taurine-induced synaptic potentiation. We show that taurine-induced potentiation is not related to the intracellular accumulation of taurine and is not impaired by 2-guanidinoethanesulphonic acid, a taurine transport inhibitor that is a substrate of taurine transporter. We have found that taurine uptake in hippocampal synaptosomes was inhibited by SKF 89976A, a GABA uptake blocker that is not transportable by GABA transporters. SKF 89976A prevents the induction of synaptic potentiation by taurine application. This effect is neither mimicked by nipecotic acid, a broad inhibitor of GABA transporters that does not affect taurine uptake, nor by NO-711, a specific and potent inhibitor of GABA transporter GAT-1. In addition, L-LTP induced by trains of high-frequency stimulation is also inhibited by SKF 89976A, and taurine, at a concentration that does not change basal synaptic transmission, overcomes such inhibition. We conclude that taurine induces synaptic potentiation through the activation of a system transporting taurine and that taurine uptake is required for the induction of synaptic plasticity phenomena such as L-LTP.