Changes in the distribution of calcium calmodulin-dependent protein kinase II at the presynaptic bouton after depolarization

Brain Cell Biol. 2006 Jun;35(2-3):117-24. doi: 10.1007/s11068-007-9012-5. Epub 2007 Sep 20.


Phosphorylation of synapsin I by CaMKII has been reported to mobilize synaptic vesicles from the reserve pool. In the present study, the distributions of alpha-CaMKII and of synapsin I were compared in synaptic boutons of unstimulated and stimulated hippocampal neurons in culture by immunogold electron microscopy. CaMKII and synapsin I are located in separate domains in presynaptic terminals of unstimulated neurons. Label for alpha -CaMKII typically surrounds synaptic vesicle clusters and is absent from the inside of the cluster in control synapses. In contrast, intense labeling for synapsin I is found within the vesicle clusters. Following 2 minutes of depolarization in high K(+), synaptic vesicles decluster and CaMKII label disperses and mingles with vesicles and synapsin I. These results indicate that, under resting conditions, CaMKII has limited access to the synapsin I in synaptic vesicle clusters. The peripheral distribution of CaMKII around vesicle clusters suggests that CaMKII-mediated declustering progresses from the periphery towards the center, with the depth of penetration into the synaptic vesicle cluster depending on the duration of CaMKII activation. Depolarization also promotes a significant increase in CaMKII immunolabel near the presynaptic active zone. Activity-induced redistribution of CaMKII leaves it in a position to facilitate phosphorylation of additional presynaptic proteins regulating neurotransmitter release.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / physiology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cells, Cultured
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Microscopy, Immunoelectron
  • Neurotransmitter Agents / metabolism*
  • Phosphorylation
  • Potassium / metabolism
  • Potassium / pharmacology
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Synapsins / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure


  • Neurotransmitter Agents
  • Synapsins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Potassium
  • Calcium