Long-term potentiation induction--a synaptic catch mechanism released by extracellular phosphorylation.
The best understood form of long-term potentiation in hippocampal CA1 neurons is induced by activation of the N-methyl-D-aspartate receptor complex and subsequent activation of the intracellular second messenger systems. In addition to this intracellular mechanism, long-term potentiation can also be induced by an extracellular mechanism involving phosphorylation by ATP-ecto-protein kinase. In the present study, we hypothesize that a putative blocking molecule of the formation of long-term potentiation exists on the synaptic membrane, and examine whether ecto-protein kinases play a role in the block of long-term potentiation by phosphorylating the ecto-domains of this molecule in CA1 neurons of guinea-pig hippocampal slices. Long-term potentiation was induced by theta burst stimulation whether or not the test input was delivered to the CA1 neurons following burst stimulation. However, 5 microM K-252b, an ecto-protein kinase inhibitor, only blocked the induction of long-term potentiation when the test input was delivered during a 30-min period following burst stimulation. The results suggest that the process of formation of long-term potentiation continues independently of test synaptic input, while the block of long-term potentiation results from a combination of an interruption of the ATP-ecto-protein kinase-dependent processes and continued test synaptic input after burst stimulation. This block of long-term potentiation, which should be released by activation of ATP-ecto-protein kinase, is suggested to act as a "safety catch" for synaptic plasticity in hippocampal CA1 neurons.
Fujii
S
S
Department of Physiology, Yamagata University School of Medicine, Yamagata, Japan. sfujii@med.id.yamagata-u.ac.jp
Kuroda
Y
Y
Ito
K
K
Kato
H
H
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects* / Q000201:enzymology*; D006168:Guinea Pigs; D026121:Indole Alkaloids; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000201:enzymology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D047428:Protein Kinase Inhibitors; C049985:staurosporine aglycone; D011494:Protein Kinases; C034454:ectoprotein kinase