N-甲基-D-天冬氨酸（NMDA）可诱导海马体中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的GluR1亚基发生长期突触抑制和去磷酸化。
NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus.
作者信息
Lee H K, Kameyama K, Huganir R L, Bear M F
机构信息
Howard Hughes Medical Institute, Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.
出版信息
Neuron. 1998 Nov;21(5):1151-62. doi: 10.1016/s0896-6273(00)80632-7.
Brief bath application of N-methyl-D-aspartate (NMDA) to hippocampal slices produces long-term synaptic depression (LTD) in CA1 that is (1) sensitive to postnatal age, (2) saturable, (3) induced postsynaptically, (4) reversible, and (5) not associated with a change in paired pulse facilitation. Chemically induced LTD (Chem-LTD) and homosynaptic LTD are mutually occluding, suggesting a common expression mechanism. Using phosphorylation site-specific antibodies, we found that induction of chem-LTD produces a persistent dephosphorylation of the GluR1 subunit of AMPA receptors at serine 845, a cAMP-dependent protein kinase (PKA) substrate, but not at serine 831, a substrate of protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaMKII). These results suggest that dephosphorylation of AMPA receptors is an expression mechanism for LTD and indicate an unexpected role of PKA in the postsynaptic modulation of excitatory synaptic transmission.
将N-甲基-D-天冬氨酸（NMDA）短暂施加于海马切片可在CA1区产生长时程突触抑制（LTD），该LTD具有以下特点：（1）对出生后年龄敏感；（2）具有饱和性；（3）由突触后诱导产生；（4）可逆；（5）与双脉冲易化的变化无关。化学诱导的LTD（化学LTD）和同突触LTD相互阻碍，提示存在共同的表达机制。使用磷酸化位点特异性抗体，我们发现化学LTD的诱导会导致AMPA受体的GluR1亚基在丝氨酸845（一种cAMP依赖性蛋白激酶（PKA）的底物）处持续去磷酸化，但在丝氨酸831（蛋白激酶C（PKC）和钙/钙调蛋白依赖性蛋白激酶II（CaMKII）的底物）处不会去磷酸化。这些结果表明，AMPA受体的去磷酸化是LTD的一种表达机制，并表明PKA在兴奋性突触传递的突触后调制中具有意想不到的作用。
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