Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches.
Regulation of glycine-insensitive desensitization of the NMDA receptor in outside-out patches.
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DOI：
10.1152/jn.1994.72.2.754
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发表时间：
1994-08
影响因子：
2.5
通讯作者：
G. Tong;Craig E. Jahr
中科院分区：
文献类型：
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作者：
G. Tong;Craig E. Jahr
1. 在培养的大鼠海马神经元的外侧斑块中研究了 N-甲基-D-天冬氨酸 (NMDA) 受体脱敏的调节。斑块切除后甘氨酸不敏感形式的脱敏逐渐增加，不需要细胞外 Ca2+ 浓度，也不依赖于使用，但斑块形成后初始脱敏程度因细胞内双-(邻氨基苯氧基)-N,N,N',N'-四乙酸 (BAPTA) 降低。 2.用30μM丹曲林预培养神经元，可以减少细胞内Ca2+的释放，也可以降低贴片切除后NMDA受体脱敏的程度。因此，这种脱敏形式的发展似乎是由细胞内钙的短暂增加引发的。 3.细胞内ATP-gamma S、高浓度磷酸酶抑制剂、微囊藻毒素或细胞内应用钙调磷酸酶肽抑制剂也可降低甘氨酸不敏感脱敏的程度。这些数据支持这样的假设：外侧斑块中 NMDA 受体的甘氨酸不敏感脱敏部分受到受体或相关蛋白的磷酸化状态的调节。 4. 由于 NMDA 通道对 Ca2+ 的渗透性很强，磷酸化的程度以及受体的脱敏可能对突触激活敏感，并且可以作为降低兴奋强度和可塑性的反馈机制。
1. Regulation of desensitization of N-methyl-D-aspartate (NMDA) receptors was studied in outside-out patches from cultured rat hippocampal neurons. The progressive increase in a glycine-insensitive form of desensitization after patch excision did not require extracellular Ca2+ concentration nor was it use dependent, but the initial extent of desensitization after patch formation was reduced by intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). 2. Preincubation of neurons with 30 microM dantrolene, which can decrease Ca2+ release from intracellular stores, also reduced the degree of NMDA receptor desensitization just after patch excision. Thus the development of this form of desensitization appears to be triggered by a transient increase of intracellular calcium. 3. The extent of glycine-insensitive desensitization was also reduced by intracellular ATP-gamma S, high concentrations of the phosphatase inhibitor, microcystin, or intracellular application of a peptide inhibitor of calcineurin. These data support the hypothesis that glycine-insensitive desensitization of the NMDA receptor in outside-out patches is regulated in part by the phosphorylation state of the receptor or an associated protein. 4. Because the NMDA channel is very permeable to Ca2+, the extent of phosphorylation and thus desensitization of the receptors may be sensitive to synaptic activation and could serve as a feedback mechanism to decrease the intensity of excitation and plasticity.