Persistent protein kinase activity underlying long-term potentiation

Malinow, R., Madison, D. V., Tsien, R. W. (October 1988) Persistent protein kinase activity underlying long-term potentiation. Nature, 335 (6193). pp. 820-4. ISSN 0028-0836 (Print)

DOI: 10.1038/335820a0


Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a much-studied example of synaptic plasticity. Although the role of N-methyl-D-aspartate (NMDA) receptors in the induction of LTP is well established, the nature of the persistent signal underlying this synaptic enhancement is unclear. Involvement of protein phosphorylation in LTP has been widely proposed, with protein kinase C (PKC) and calcium-calmodulin kinase type II (CaMKII) as leading candidates. Here we test whether the persistent signal in LTP is an enduring phosphoester bond, a long-lived kinase activator, or a constitutively active protein kinase by using H-7, which inhibits activated protein kinases and sphingosine, which competes with activators of PKC (ref. 17) and CaMKII (ref. 18). H-7 suppressed established LTP, indicating that the synaptic potentiation is sustained by persistent protein kinase activity rather than a stably phosphorylated substrate. In contrast, sphingosine did not inhibit established LTP, although it was effective when applied before tetanic stimulation. This suggests that persistent kinase activity is not maintained by a long-lived activator, but is effectively constitutive. Surprisingly, the H-7 block of LTP was reversible; evidently, the kinase directly underlying LTP remains activated even though its catalytic activity is interrupted indicating that such kinase activity does not sustain itself simply through continual autophosphorylation (see refs 9, 13, 15).

Item Type: Paper
Uncontrolled Keywords: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Animals Binding, Competitive Calcium/pharmacology Calmodulin/pharmacology Electrophysiology Enzyme Activation/drug effects Hippocampus/*physiology Isoquinolines/pharmacology Phorbol Esters/pharmacology Phosphorylation Piperazines/pharmacology Protein Kinase C/metabolism Protein Kinase Inhibitors Protein Kinases/*metabolism Rats Receptors, N-Methyl-D-Aspartate Receptors, Neurotransmitter/physiology Sphingosine/pharmacology Synapses/*physiology Synaptic Transmission
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Malinow lab
Depositing User: Gail Sherman
Date: 27 October 1988
Date Deposited: 29 Sep 2017 14:58
Last Modified: 29 Sep 2017 14:58
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