Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons.
Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons.
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DOI：
10.1152/jn.1995.73.1.427
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发表时间：
1995
影响因子：
2.5
通讯作者：
Christian Rosenmund;A. Feltz;G. Westbrook
中科院分区：
文献类型：
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作者：
Christian Rosenmund;A. Feltz;G. Westbrook
1. 我们通过将兴奋性突触后电流 (EPSC) 与之前描述的全细胞 NMDA 电流的钙依赖性调节进行比较，检查了培养的海马神经元中突触激活的 N-甲基-D-天冬氨酸 (NMDA) 受体是否受到细胞内钙的调节。使用标准的全细胞记录和快速应用方法。 2. 在 2-氨基-5-磷酸戊酸 (AP5) 存在的情况下，低频 (0.2 Hz) 刺激 EPSC 引起恒定振幅的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 受体介导的 EPSC。在含 Ca(2+) 的溶液中去除 AP5 后，缓慢的 NMDA 受体介导的 EPSC 的幅度在接下来的 10 次刺激期间下降了约 50%。 EPSC的减少取决于细胞外钙浓度和刺激频率，与突触后NMDA受体的Ca(2+)依赖性脱敏/失活一致。在含 Ca(2+) 溶液中使用 NMDA（10 µM，10 s）进行全细胞预脉冲，可将缓慢的 EPSC 抑制至类似程度。一系列缓慢的 EPSC 还产生低钙溶液中引起的全细胞 NMDA 电流的 Ca(2+) 依赖性失活。 3. 这些结果表明，突触 NMDA 受体被细胞内钙灭活，并且钙通过突触激活的 NMDA 受体进入足以提供缓慢 EPSC 的反馈抑制。
1. We examined whether synaptically activated N-methyl-D-aspartate (NMDA) receptors are regulated by intracellular calcium in cultured hippocampal neurons by comparing excitatory postsynaptic currents (EPSCs) to the previously described calcium-dependent regulation of whole cell NMDA currents. Standard whole cell recording and fast application methods were used. 2. Low-frequency (0.2 Hz) stimulation of EPSCs in the presence of 2-amino-5-phosphonovalerate (AP5) evoked a constant amplitude alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSC. On removal of AP5 in Ca(2+)-containing solutions, the amplitude of the slow NMDA receptor-mediated EPSC decreased by approximately 50% during the next 10 stimuli. The decrease in the EPSC was dependent on the extracellular calcium concentration and stimulus frequency, consistent with Ca(2+)-dependent desensitization/inactivation of postsynaptic NMDA receptors. A whole cell prepulse of NMDA (10 microM, 10 s) in Ca(2+)-containing solutions inhibited the slow EPSC to a similar degree. A series of slow EPSCs also produced Ca(2+)-dependent inactivation of whole cell NMDA currents evoked in low calcium solutions. 3. These results demonstrate that synaptic NMDA receptors are inactivated by intracellular calcium and that calcium entry through synaptically activated NMDA receptors is sufficient to provide feedback inhibition of the slow EPSC.