目的:观察在发育大鼠视皮层脑片标本上D-丝氨酸对大鼠视皮层神经元突触后NMDA受体功能是否具有调制作用.方法:应用脑片膜片钳全细胞记录技术,记录13-15 d SD大鼠视皮层Ⅱ/Ⅲ层椎体神经元的微小兴奋性突触后电流(mEPSCs),观察D-丝氨酸对mEPSCs的调制作用.结果:mEPSCs包含两种受体电流成分,即AMPA受体与NMDA受体电流成分;应用外源性D.丝氨酸(1,10和100μmol/L)均增强了mEPScs的NMDA受体电流成分(P<0.01),并呈现浓度依赖性,而应用NMDA受体阻断剂D-APV(50μmol/L)完全阻断这种增强效应.此外,D-丝氨酸没有影响mEPSCs的AMPA受体电流成分.结论:在大鼠视皮层Ⅱ/Ⅲ层锥体神经元上,突触后NMDA受体的甘氨酸结合位点是不饱和的,应用外源性D-丝氨酸可以增强NMDA受体功能,本研究为精神分裂等精神疾病的治疗提供有意义的资料.
D-serine modulates the postsynaptic NMDA receptor responses in the rat visual cortex
AIM: To investigate whether D-serine modulates the postsynaptic NMDA receptor responses in the rat visual cortex. METHODS: Whole cell patch-clamp recordings were used to record miniature excitatory postsynaptic currents (mEPSCs) from neurons in the visual cortex slices prepared from Sprague-Dawley rats aged 13-15 d. Then we examined whether exogenously applied D-serine modulates postsynaptic NMDA receptor responses. RESULTS: The mEPSCs were comprised of both NMDA and AMPA receptor-mediated components. Application of exogenous D-serine(1, 10 and 100 μmol/L) potentiated the NMDA receptor-mediated mEPSCs in a dose-dependent manner(P ＜ 0. 01), which was abolished by D-APV (50 μmol/L). CONCLUSION: These results indicate that the glycine binding sites on postsynaptic NMDA-Rs are not normally saturated. Exogenous D-serine can act on glycine binding sites at postsynaptic NMDA receptors to enhance NMDA receptor function.
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