Department of Neuroscience and Physiology and.
Department of Neuroscience and Physiology and Department of Neurosurgery, New York University School of Medicine, New York, New York 10016
J Neurosci. 2015 Jan 21;35(3):873-7. doi: 10.1523/JNEUROSCI.2293-14.2015.
The plasma membrane Ca(2+)-ATPase (PMCA) is found near postsynaptic NMDARs. This transporter is a Ca(2+)-H(+) exchanger that raises cell surface pH. We tested whether the PMCA acts in an autocrine fashion to boost pH-sensitive, postsynaptic NMDAR currents. In mouse hippocampal slices, NMDAR EPSCs in a singly activated CA1 pyramidal neuron were reduced when buffering was augmented by exogenous carbonic anhydrase (XCAR). This effect was blocked by the enzyme inhibitor benzolamide and mimicked by the addition of HEPES buffer. Similar EPSC reduction occurred when PMCA activation was prevented by dialysis of BAPTA or the PMCA inhibitor carboxyeosin. Using HEPES, BAPTA, or carboxyeosin, the effect of XCAR was completely occluded. XCAR similarly curtailed NMDAR EPSCs of minimal amplitude, but had no effect on small AMPAR responses. These results indicate that a significant fraction of the postsynaptic NMDAR current is reliant on a perisynaptic extracellular alkaline shift generated by the PMCA.
质膜 Ca(2+)-ATP 酶（PMCA）位于突触后 NMDA 受体附近。这种转运蛋白是一种 Ca(2+)-H(+)交换器，可提高细胞表面 pH 值。我们测试了 PMCA 是否以自分泌的方式增强 pH 敏感的突触后 NMDA 受体电流。在小鼠海马切片中，当通过外源性碳酸酐酶 (XCAR) 增强缓冲作用时，单个激活的 CA1 锥体神经元中的 NMDA 受体 EPSC 减少。该效应被酶抑制剂苯甲酰胺阻断，并被 HEPES 缓冲液模拟。当通过 BAPTA 透析或 PMCA 抑制剂羧基肌球蛋白阻止 PMCA 激活时，会发生类似的 EPSC 减少。使用 HEPES、BAPTA 或羧基肌球蛋白，XCAR 的作用完全被阻断。XCAR 同样会抑制最小幅度的 NMDA 受体 EPSC，但对小的 AMPAR 反应没有影响。这些结果表明，突触后 NMDA 受体电流的很大一部分依赖于 PMCA 产生的周围细胞外碱性偏移。
