CHANNEL KINETICS DETERMINE THE TIME COURSE OF NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS
CHANNEL KINETICS DETERMINE THE TIME COURSE OF NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS
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DOI：
10.1038/346565a0
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发表时间：
1990-08-09
期刊：
影响因子：
64.8
通讯作者：
JAHR, CE
中科院分区：
文献类型：
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作者：
LESTER, RAJ;CLEMENTS, JD;JAHR, CE
谷氨酸的突触释放导致许多脊椎动物中枢突触产生双组分兴奋性突触后电流（e.p.s.c） 1 - 6。非n-甲基- d -天冬氨酸受体介导的组分具有快速起效和衰减，而n-甲基- d -天冬氨酸（NMDA）受体介导的组分具有缓慢的上升时间和数百毫秒的衰减，比NMDA通道平均打开时间长100倍[7 - 9]。NMDA介导的e.p.s.c.的缓慢衰退可能是由于突触间隙中残留的谷氨酸导致NMDA受体的反复结合和激活。然而，在培养的海马神经元中，我们发现NMDA受体拮抗剂d -2-氨基-5-磷酸戊酸酯在突触激活后快速应用对慢速e.p.s.c.没有影响，这表明谷氨酸没有发生再结合。此外，谷氨酸向外膜斑块的短暂脉冲导致NMDA通道的开放持续数百毫秒，表明谷氨酸可以在这段时间内保持结合。这些结果表明，突触间隙中短暂的谷氨酸脉冲足以解释慢速的e.p.s.c。
SYNAPTIC release of glutamate results in a two component excitatory postsynaptic current (e.p.s.c.) at many vertebrate central synapses1–6. Non-N-methyl-D-aspartate receptors mediate a component that has a rapid onset and decay while the component mediated byN-methyl-D-aspartate (NMDA) receptors has a slow rise-time and a decay of several hundred milliseconds, 100 times longer than the mean open time of NMDA channels7–9. The slow decay of the NMDA-mediated e.p.s.c. could be due to residual glutamate in the synaptic cleft resulting in repeated binding and activation of NMDA receptors. However, in cultured hippocampal neurons, we find that the NMDA receptor antagonist D-2-amino-5-phosphonopentanoate has no effect on the slow e.p.s.c. when rapidly applied after activation of the synapse, suggesting that rebinding of glutamate does not occur. In addition, a brief pulse of glutamate to an outside-out membrane patch results in openings of NMDA channels that persist for hundreds of milliseconds, indicating that glutamate can remain bound for this period. These results imply that a brief pulse of glutamate in the synaptic cleft is sufficient to account for the slow e.p.s.c.