Abstract
CA2+-regulated protein kinases play critical roles in long-term potentiation (LTP). To understand the role of Ca2+/calmodulin (CaM) signaling pathways in synaptic transmission better, Ca2+/CaM was injected into hippocampal CA1 neurons. Ca2+/CaM induced significant potentiation of excitatory synaptic responses, which was blocked by coinjection of a CaM-binding peptide and was not induced by injections of Ca2+ or CaM alone. Reciprocal experiments demonstrated that Ca2+/CaM-induced synaptic potentiation and tetanus-induced LTP occluded one another. Pseudosubstrate inhibitors or high-affinity substrates of CaMKII or PKC blocked Ca2/CaM-induced potentiation, indicating the requirement of CaMKII and PKC activities in synaptic potentiation. We suggest that postsynaptic levels of free Ca2+/CaM is a rate limiting factor and that functional cross-talk between Ca2+/CaM and PKC pathways occurs during the induction of LTP.
Publication types
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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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Amino Acid Sequence
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Animals
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Calcium / 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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Calmodulin / pharmacology*
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Calmodulin-Binding Proteins / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / physiology
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Electric Stimulation
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Long-Term Potentiation / drug effects*
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Male
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Membrane Potentials / drug effects
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Molecular Sequence Data
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Nerve Tissue Proteins / pharmacology
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Neurogranin
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Patch-Clamp Techniques
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Peptide Fragments / pharmacology
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Phosphorylation / drug effects
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Protein Kinase C / pharmacology
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Protein Kinase C / physiology*
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Protein Processing, Post-Translational / drug effects
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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Signal Transduction / physiology*
Substances
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Calmodulin
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Calmodulin-Binding Proteins
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Nerve Tissue Proteins
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Nrgn protein, rat
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Peptide Fragments
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Neurogranin
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Calcium