Casey M, Maguire C, Kelly A, Gooney M A, Lynch M A
Physiology Department, Trinity College, Dublin, Ireland.
Hippocampus. 2002;12(3):377-85. doi: 10.1002/hipo.10036.
A great deal of recent evidence points to a role for tyrosine kinase in expression of LTP. Data have been presented that are consistent with the idea that tyrosine phosphorylation of proteins occurs in both the presynaptic and postsynaptic areas. In this study, we set out to investigate the role that tyrosine kinase might play presynaptically to modulate release of glutamate in an effort to understand the mechanism underlying the persistent increase in release that accompanies LTP in perforant path-granule cell synapses. We report that LTP was associated with increased calcium influx and glutamate release. LTP was also associated with an increase in phosphorylation of the alpha-subunit of calcium channels and ERK in synaptosomes prepared from dentate gyrus, and these effects were inhibited when LTP was blocked by the tyrosine kinase inhibitor, genistein. LTP was accompanied by increased protein synthesis and increased phosphorylation of CREB in entorhinal cortex, effects that were also blocked by genistein. We conclude that tetanic stimulation leads to enhanced tyrosine phosphorylation of certain presynaptically located proteins that modulate glutamate release and contribute to expression of LTP.
近期大量证据表明酪氨酸激酶在长时程增强（LTP）的表达中发挥作用。已有数据表明，蛋白质的酪氨酸磷酸化发生在突触前和突触后区域，这一观点是一致的。在本研究中，我们着手研究酪氨酸激酶在突触前可能发挥的作用，以调节谷氨酸的释放，从而了解在穿通通路-颗粒细胞突触中伴随LTP出现的递质释放持续增加的潜在机制。我们报告称，LTP与钙内流增加和谷氨酸释放增加有关。LTP还与从齿状回制备的突触体中钙通道α亚基和细胞外信号调节激酶（ERK）的磷酸化增加有关，当酪氨酸激酶抑制剂金雀异黄素阻断LTP时，这些效应受到抑制。LTP伴随着内嗅皮质中蛋白质合成增加和cAMP反应元件结合蛋白（CREB）磷酸化增加，这些效应也被金雀异黄素阻断。我们得出结论，强直刺激导致某些位于突触前的蛋白质酪氨酸磷酸化增强，这些蛋白质调节谷氨酸释放并有助于LTP的表达。
