Sihra T S, Nairn A C, Kloppenburg P, Lin Z, Pouzat C
Department of Pharmacology, Royal Free Hospital School of Medicine, University of London, U.K.
Biochem Biophys Res Commun. 1995 Jul 17;212(2):609-16. doi: 10.1006/bbrc.1995.2013.
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.
先前的研究表明，4-氨基吡啶（4AP）诱导的钙离子内流会影响从大鼠大脑皮层分离出的神经末梢（突触体）释放谷氨酸。我们现在发现，用免疫抑制剂FK506（一种蛋白磷酸酶-2B（钙调神经磷酸酶）的抑制剂）预孵育突触体后，这种释放的钙依赖性成分会增强。FK506并不抑制谷氨酸从胞质池的非钙依赖性释放。研究FK506对4AP引发的钙离子内流的影响表明，抑制钙调神经磷酸酶的活性会导致电压依赖性钙离子内流增加。基于这些结果，我们认为钙调神经磷酸酶介导的蛋白质去磷酸化可能会抑制电压依赖性钙通道的活性，从而抑制诱发的谷氨酸释放。初始钙离子内流产生的钙调神经磷酸酶激活可能代表一种负反馈，以限制与谷氨酸释放相关的钙通道的活性。
