Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Mol Brain. 2018 Oct 25;11(1):62. doi: 10.1186/s13041-018-0406-3.
N-Methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are two major types of ionotropic glutamate receptors involved in synaptic transmission. However, excessive activity of these receptors can be cytotoxic and thus their function must be precisely controlled. We have previously reported that NMDA receptor activity is dysregulated following genetic knockout of cellular prion protein (PrP), and that PrP regulation of NMDA receptors is copper-dependent. Here, we employed electrophysiological methods to study NMDAR and AMPAR currents of cultured hippocampal neurons from PrP overexpresser mice. We show that NMDA receptor current amplitude and kinetics are differentially modulated by overexpression of human or mouse PrP. By contrast, AMPA receptor activity was unaffected. Nonetheless, AMPA receptor activity was modulated by copper ions in a manner similar to what we previously reported for NMDA receptors. Taken together, our findings reveal that AMPA and NMDA receptors are differentially regulated by PrP, but share common modulation by copper ions.
N-甲基-D-天冬氨酸受体 (NMDARs) 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPARs) 是参与突触传递的两种主要类型的离子型谷氨酸受体。然而，这些受体的过度活动可能具有细胞毒性，因此必须对其功能进行精确控制。我们之前曾报道过，在细胞朊病毒蛋白 (PrP) 基因敲除后，NMDA 受体活性会失调，而 PrP 对 NMDA 受体的调节依赖于铜。在这里，我们采用电生理学方法研究了过表达 PrP 的小鼠海马神经元培养物中的 NMDAR 和 AMPAR 电流。我们表明，过表达人或鼠 PrP 可不同程度地调节 NMDA 受体电流幅度和动力学。相比之下，AMPA 受体活性不受影响。尽管如此，铜离子以与我们之前报道的 NMDA 受体相似的方式调节 AMPA 受体活性。总之，我们的研究结果表明，PrP 对 AMPA 和 NMDA 受体的调节存在差异，但对铜离子的调节存在共同机制。
