Chronic NMDA receptor antagonism during retinotopic map formation depresses CaM kinase II differentiation in rat superior colliculus.
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.
Scheetz
A J
AJ
Yale University, Department of Biology, New Haven, CT 06520, USA.
Prusky
G T
GT
Constantine-Paton
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D001931:Brain Mapping; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D009475:Neurons, Afferent / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012160:Retina / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity; D013477:Superior Colliculi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D014795:Visual Pathways / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases