PRESYNAPTIC AND POSTSYNAPTIC GLUTAMATE RECEPTORS AT A GIANT EXCITATORY SYNAPSE IN RAT AUDITORY BRAIN-STEM SLICES
PRESYNAPTIC AND POSTSYNAPTIC GLUTAMATE RECEPTORS AT A GIANT EXCITATORY SYNAPSE IN RAT AUDITORY BRAIN-STEM SLICES
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DOI：
10.1113/jphysiol.1995.sp020974
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发表时间：
1995-10-15
影响因子：
5.5
通讯作者：
FORSYTHE, ID
中科院分区：
文献类型：
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作者：
BARNESDAVIES, M;FORSYTHE, ID
1. 采用全细胞膜片记录技术，观察了在梯形体内侧核神经元中由Held花萼产生的EPSC。每个神经元接受来自单个花萼（巨突触）的体细胞输入。NMDA受体介导的慢速EPSC在10 ms内达到峰值，并以双指数衰减，时间常数分别为44和147 ms。快速EPSC的平均上升时间为356 μ s（25℃），而衰减用双指数描述，时间常数为0.70和3.43 ms.3。环噻嗪减缓了快速EPSC的衰变，表明它是由AMPA受体介导的。较慢的时间常数比较快的时间常数减速的程度更大。环噻嗪增强EPSC振幅，部分是通过突触前机制。代谢性谷氨酸受体（mGluR）激动剂1S、3S-ACPD、1S、3R-ACPD和l -2-氨基-4-磷酸丁酸酯（L-AP4）可逆性抑制EPSC振幅。1S、3S-ACPD的剂量-反应曲线显示EC（50）为7 μ M， Hill系数为1.2.5。变异比系数分析表明，上述mGluR激动剂作用于突触前，降低了递质释放的概率。腺苷和巴氯芬也通过突触前机制抑制传递。α -甲基-4-羧基苯基甘氨酸（MCPG; 0.5-1 mM）不拮抗1S、3S-ACPD的作用，而高浓度的l- 2-氨基-3-磷酸丙酸（L-AP3; 1 mM）和4-羧基-3-羟基苯基甘氨酸（4C3HPG; 500 μ M）抑制了传播。[Ca2+](o)与EPSC振幅呈幂函数关系，协同作用值在1.5 ~ 3.4.8之间。mGluR调节递质释放的机制似乎与突触前Ca2+或K+电流无关，因为ACPD没有引起配对脉冲促进水平或突触前动作电位持续时间的变化（通过末端直接记录观察），这表明突触前mGluR转导机制可能与部分胞外机制耦合。我们的数据与任何已知的mGluR亚型的花萼存在不一致。快速EPSC的时间过程和药理学与克隆AMPA受体数据的比较与GluR-D-o亚基主导突触后通道的观点一致。
1. Whole-cell patch recordings were used to examine the EPSC generated by the calyx of Held in neurones of the medial nucleus of the trapezoid body (MNTB). Each neurone receives a somatic input from a single calyx (giant synapse).2. A slow NMDA receptor-mediated EPSC peaked in 10 ms and decayed as a double exponential with time constants of 44 and 147 ms. A fast EPSC had a mean rise time of 356 mu s (at 25 degrees C), while the decay was described by a double exponential with time constants of 0.70 and 3.43 ms.3. Cyclothiazide slowed the decay of the fast EPSC, indicating that it is mediated by AMPA receptors. The slower time constant was slowed to a greater extent than the faster time constant. Cyclothiazide potentiated EPSC amplitude, partly by a presynaptic mechanism.4. The metabotropic glutamate receptor (mGluR) agonists, 1S,3S-ACPD, 1S,3R-ACPD and L-2-amino-4-phosphonobutyrate (L-AP4) reversibly depressed EPSC amplitude. A dose-response curve for 1S,3S-ACPD gave an EC(50) of 7 mu M and a Hill coefficient of 1.2.5. Analysis of the coefficient of variation ratio showed that the above mGluR agonists acted presynaptically to reduce the probability of transmitter release. Adenosine and baclofen also depressed transmission by a presynaptic mechanism.6. alpha-Methyl-4-carboxyphenylglycine (MCPG; 0.5-1 mM) did not antagonize the effects of 1S,3S-ACPD, while high concentrations of L-2-amino-3-phosphonopropionic acid (L-AP3; 1 mM) and 4-carboxy-3-hydroxyphenylglycine (4C3HPG; 500 mu M) depressed transmission.7. There was a power relationship between [Ca2+](o) and EPSC amplitude with co-operativity values ranging from 1.5 to 3.4.8. The mechanism by which mGluRs modulate transmitter release appeared to be independent of presynaptic Ca2+ or K+ currents, since ACPD caused no change in the level of paired-pulse facilitation or the duration of the presynaptic action potential (observed by direct recording from the terminal), indicating that the presynaptic mGluR transduction mechanism may be coupled to part of the exocytotic machinery.9. Our data are not consistent with the presence at the calyx of Held of any one known mGluR subtype. Comparison of the time course and pharmacology of the fast EPSC with data from cloned AMPA receptors is consistent with the idea that GluR-D-o subunits dominate the postsynaptic channels.