Decreases in CaMKII activity trigger persistent potentiation of intrinsic excitability in spontaneously firing vestibular nucleus neurons

Neuron. 2005 May 19;46(4):623-31. doi: 10.1016/j.neuron.2005.04.009.

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a biochemical switch that is turned on by increases in intracellular calcium to mediate synaptic plasticity. Here, we show that reductions in CaMKII activity trigger persistent increases in intrinsic excitability. In spontaneously firing vestibular nucleus neurons, CaMKII activity is near maximal, and blockade of CaMKII activity increases excitability by reducing BK-type calcium-activated potassium currents. Firing rate potentiation, a form of plasticity in which synaptic inhibition induces long-lasting increases in excitability, is occluded by prior blockade of CaMKII and blocked by addition of constitutively active CaMKII. Reductions in CaMKII activity are necessary and sufficient to induce firing rate potentiation and may contribute to motor learning in the vestibulo-ocular reflex.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Action Potentials / radiation effects
  • Animals
  • Animals, Newborn
  • Blotting, Western / methods
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology
  • Statistics, Nonparametric
  • Time Factors
  • Vestibular Nuclei / cytology*

Substances

  • Enzyme Inhibitors
  • Peptide Fragments
  • Peptides
  • KN 62
  • iberiotoxin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium