A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release.
A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release.
复制标题
钙调神经磷酸酶（蛋白磷酸酶-2B）在调节谷氨酸释放中的作用。
DOI：
10.1006/bbrc.1995.2013
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发表时间：
1995
影响因子：
3.1
通讯作者：
Christophe Pouzat
中科院分区：
文献类型：
--
作者：
T. Sihra;A. Nairn;Peter Kloppenburg;Zhixin Lin;Christophe Pouzat
以往的研究表明，4-氨基吡啶（4-aminopyridine，4AP）诱导的钙内流影响从大鼠大脑皮层分离的神经末梢（突触体）释放谷氨酸。我们现在表明，这种释放的钙依赖性成分是增强预孵育的突触体与免疫抑制剂，FK 506，蛋白磷酸酶-2B（calcineurin）的抑制剂。FK 506不抑制谷氨酸从胞质池中的钙非依赖性释放。FK 506对4AP引起的Ca内流的影响的检查表明，钙调神经磷酸酶活性的抑制导致电压依赖性Ca内流的增加。基于这些结果，我们认为，钙调磷酸酶影响的蛋白质去磷酸化可能会抑制电压依赖性钙通道的活动，并在这样做抑制诱发谷氨酸释放。初始钙离子进入产生的钙调磷酸酶的激活可能代表一种负反馈，以限制与谷氨酸释放偶联的钙通道的活性。
Previous studies have shown that 4-aminopyridine (4AP) induced Ca-influx effects the release of glutamate from nerve terminals (synaptosomes) isolated from rat cerebral cortex. We now show that the Ca-dependent component of this release is potentiated by preincubation of the synaptosomes with the immunosuppressant, FK506, an inhibitor of protein phosphatase-2B (calcineurin). FK506 did not inhibit the Ca-independent release of glutamate from a cytosolic pool. Examination of the effect of FK506 on the influx of Ca elicited by 4AP indicated that inhibition of calcineurin activity resulted in an increase of voltage-dependent Ca-influx. Based on these results, we suggest that protein dephosphorylation effected by calcineurin may suppress voltage-dependent Ca-channel activity and in so doing inhibits evoked glutamate release. Activation of calcineurin produced by initial Ca-entry may represent a negative feedback to limit the activity of Ca-channels coupled to the release of glutamate.