Abstract
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is very critical for synaptic plasticity and memory formation. Although significant progress has been made in understanding the role of postsynaptic CaMKII in synaptic plasticity, very little is known about its presynaptic function during plasticity changes. Here we report that KN-93, a membrane-permeable CaMKII inhibitor, blocked glutamate-induced increases in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and the number of presynaptic functional boutons in cultured hippocampal pyramidal neurons. In addition, presynaptic injection of the membrane-impermeable CaMKII inhibitor peptide 281-309 blocked synaptic plasticity induced by tetanus, glutamate, or NO/cGMP pathway activation as expressed by long-lasting increases in EPSC amplitude and functional presynaptic boutons. Presynaptic injection of CaMKII itself coupled with weak tetanus produced an immediate and long-lasting enhancement of EPSC amplitude. Thus, the present results conclusively prove that presynaptic CaMKII is essential for synaptic plasticity in cultured hippocampal neurons.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Animals, Newborn
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Benzylamines / pharmacology
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Interactions
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Electric Stimulation / methods
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Electrophysiology / methods
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Glutamic Acid / pharmacology
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Green Fluorescent Proteins
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Hippocampus / cytology*
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Hippocampus / drug effects
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Luminescent Proteins / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Inbred Strains
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Neurons / drug effects
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Neurons / physiology*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / physiology*
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Sulfonamides / pharmacology
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Time Factors
Substances
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Benzylamines
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Luminescent Proteins
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Sulfonamides
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KN 93
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Green Fluorescent Proteins
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Glutamic Acid
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2-Amino-5-phosphonovalerate
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases