Block of synapse formation between cerebral cortical neurons by a protein kinase inhibitor.
Synchronized Ca2+ transients in cultured hippocampal neurons reflect the pattern of underlying electrical activity. Here we demonstrate a similar synchronization of cerebral cortical neurons in culture, and show that this functional coupling is correlated to the appearance of morphologically identified synapses using electron microscopy. During screening of a series of drugs for inhibition of in vitro synaptogenesis, the continuous presence of a protein kinase inhibitor (K-252b) in the culture medium was found to block the synchronous firing and to decrease significantly the number of morphologically identifiable synapses. Since K-252b does not permeate the cell membrane, the results strongly suggest that phosphorylation of cell surface protein(s) by a K-252b sensitive-protein kinase is an essential process in synapse formation.
Kuroda
Y
Y
Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Ichikawa
M
M
Muramoto
K
K
Kobayashi
K
K
Matsuda
Y
Y
Ogura
A
A
Kudo
Y
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D026121:Indole Alkaloids; D008854:Microscopy, Electron; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure
D002227:Carbazoles; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone; D011493:Protein Kinase C; D002118:Calcium