Fujii Satoshi
Department of Physiology, Yamagata University School of Medicine, Japan.
J Pharmacol Sci. 2004 Feb;94(2):103-6. doi: 10.1254/jphs.94.103.
Application of 10 microM ATP for 10 min transiently depressed, then slowly augmented, synaptic transmission in CA1 neurons, leading to long-term potentiation (LTP) (ATP-induced LTP). This ATP-induced LTP was blocked by addition of an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, D,L-2-amino-5-phosphonovalerate (5 microM). For ATP-induced LTP, delivery of test synaptic inputs once every 20 s to CA1 neurons could be substituted by application of 100 nM NMDA during ATP perfusion. In addition, ATP-induced LTP was blocked by co-application of an ecto-protein kinase inhibitor, K-252b (40 nM), whereas a P2X purinoceptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid 4-sodium (50 microM), or a P2Y purinoceptor antagonist, basilen blue (10 microM), had no effect. These results, therefore, indicate that the mechanisms of ATP-induced LTP involve the modulation of NMDA receptors / Ca(2+) channels and the phosphorylation of extracellular domains of synaptic membrane proteins, one of which could be the NMDA receptor / Ca(2+) channel.
应用10微摩尔ATP 10分钟，可使CA1神经元的突触传递先短暂抑制，然后缓慢增强，导致长时程增强（LTP）（ATP诱导的LTP）。这种ATP诱导的LTP可被添加N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂D，L-2-氨基-5-磷酸戊酸（5微摩尔）所阻断。对于ATP诱导的LTP，在ATP灌注期间，每20秒向CA1神经元递送一次测试突触输入可被应用100纳摩尔NMDA所替代。此外，ATP诱导的LTP可被胞外蛋白激酶抑制剂K-252b（40纳摩尔）共同应用所阻断，而P2X嘌呤受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2'，4'-二磺酸四钠（50微摩尔）或P2Y嘌呤受体拮抗剂碱性蓝（10微摩尔）则无作用。因此，这些结果表明，ATP诱导LTP的机制涉及NMDA受体/Ca(2+)通道的调节以及突触膜蛋白胞外结构域的磷酸化，其中之一可能是NMDA受体/Ca(2+)通道。
