Scheetz A J, Prusky G T, Constantine-Paton M
Yale University, Department of Biology, New Haven, CT 06520, USA.
Eur J Neurosci. 1996 Jul;8(7):1322-8. doi: 10.1111/j.1460-9568.1996.tb01594.x.
We examined the effects of chronic NMDA receptor antagonism on the normal postnatal differentiation of calcium- and calmodulin-dependent kinase II (CaM kinase II) in the rat superior colliculus. At postnatal day (P) zero, most CaM kinase II protein, as well as CaM kinase II activity, was detected in the soluble fraction. In vitro phosphorylation of P0 superior colliculus revealed several prominent substrates in both the particulate and soluble fractions. At P19 there was more particulate enzyme than soluble enzyme, and CaM kinase II activity in the particulate fraction was higher than in P0 particulate tissue. Additionally, in vitro phosphorylation of P19 superior colliculus revealed many more CaM kinase II substrates. Chronic NMDA receptor antagonism with 2-amino-5-phosphonovalerate (DL-AP5) caused CaM kinase II to retain many of the characteristics of the enzyme found in P0 untreated superior colliculus. In P19 superior colliculus treated with LD-AP5 from birth, most of the protein was in the soluble fraction, CaM kinase II activity was largely restricted to the soluble fraction, and only a few substrates were observed by in vitro phosphorylation. These effects were not observed in tissue treated with the inactive isomer, L-AP5. These results suggest that synaptic maturation is slowed by antagonism of NMDA receptors during retinotopic map formation.
我们研究了慢性N-甲基-D-天冬氨酸（NMDA）受体拮抗作用对大鼠上丘中钙调蛋白依赖性激酶II（CaM激酶II）正常产后分化的影响。在出生后第（P）0天，大部分CaM激酶II蛋白以及CaM激酶II活性在可溶部分被检测到。P0上丘的体外磷酸化显示在颗粒部分和可溶部分均有几种突出的底物。在P19时，颗粒酶比可溶酶更多，并且颗粒部分的CaM激酶II活性高于P0颗粒组织中的活性。此外，P19上丘的体外磷酸化显示出更多的CaM激酶II底物。用2-氨基-5-磷酸戊酸（DL-AP5）进行慢性NMDA受体拮抗作用使CaM激酶II保留了许多在未经处理的P0上丘中发现的酶的特征。在从出生就用LD-AP5处理的P19上丘中，大部分蛋白质存在于可溶部分，CaM激酶II活性主要局限于可溶部分，并且通过体外磷酸化仅观察到少数底物。在用无活性异构体L-AP5处理的组织中未观察到这些效应。这些结果表明在视网膜拓扑图形成过程中，NMDA受体拮抗作用会减缓突触成熟。
