Postsynaptic injection of CA2+/CaM induces synaptic potentiation requiring CaMKII and PKC activity

Neuron. 1995 Aug;15(2):443-52. doi: 10.1016/0896-6273(95)90048-9.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology*
  • Calmodulin / pharmacology*
  • Calmodulin-Binding Proteins / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Electric Stimulation
  • Long-Term Potentiation / drug effects*
  • Male
  • Membrane Potentials / drug effects
  • Molecular Sequence Data
  • Nerve Tissue Proteins / pharmacology
  • Neurogranin
  • Patch-Clamp Techniques
  • Peptide Fragments / pharmacology
  • Phosphorylation / drug effects
  • Protein Kinase C / pharmacology
  • Protein Kinase C / physiology*
  • Protein Processing, Post-Translational / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • Calmodulin
  • Calmodulin-Binding Proteins
  • Nerve Tissue Proteins
  • Nrgn protein, rat
  • Peptide Fragments
  • Neurogranin
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium