Distinct synaptic loci of Ca2+/calmodulin-dependent protein kinase II necessary for long-term potentiation and depression.
1. Extracellular bath application of the selective Ca2+/calmodulin-dependent kinase II (CaMKII) inhibitor KN-62 to hippocampal slices in vitro blocked the induction of long-term depression (LTD) by low-frequency Schaffer collateral stimulation (1 Hz/15 min) of the same concentration as has been shown previously to prevent induction of long-term potentiation (LTP) at these synapses. 2. In contrast, postsynaptic intracellular infusion of KN-62 into single CA1 pyramidal neurons did not prevent induction of LTD, although it was quite effective in blocking LTP. 3. We conclude that there is a presynaptic CaMKII that must be activated to induce LTD, whereas postsynaptic CaMKII stimulation is needed to evoke LTP. 4. Bath application of KN-62 also blocked depotentiation by low-frequency stimuli of previously induced LTP, suggesting that induction of depotentiation and de novo LTD may require the same CaMKII-dependent mechanisms.
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure
D004791:Enzyme Inhibitors; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases