Regulation of ion channel localization and phosphorylation by neuronal activity

Nat Neurosci. 2004 Jul;7(7):711-8. doi: 10.1038/nn1260. Epub 2004 Jun 13.

Abstract

Voltage-dependent Kv2.1 K(+) channels, which mediate delayed rectifier Kv currents (I(K)), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability. Here we report activity-dependent changes in the localization and biophysical properties of Kv2.1. In the kainate model of continuous seizures in rat, we find a loss of Kv2.1 clustering in pyramidal neurons in vivo. Biochemical analysis of Kv2.1 in the brains of these rats shows a marked dephosphorylation of Kv2.1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of I(K). An influx of Ca(2+) leading to calcineurin activation is both necessary and sufficient for these effects. Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cadmium Chloride / pharmacology
  • Calcimycin / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Cell Count
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Delayed Rectifier Potassium Channels
  • Dendrites / drug effects
  • Dendrites / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / pharmacology*
  • Hippocampus / cytology
  • Ion Channel Gating / drug effects*
  • Ionophores / pharmacology
  • Kainic Acid / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nitrendipine / pharmacology
  • Nitriles
  • Okadaic Acid / pharmacology
  • Patch-Clamp Techniques / methods
  • Phosphoprotein Phosphatases / pharmacology
  • Phosphorylation / drug effects
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Potassium Chloride / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Pyrethrins / pharmacology
  • Rats
  • Seizures / chemically induced
  • Seizures / physiopathology
  • Shab Potassium Channels
  • Time Factors
  • Translocation, Genetic / drug effects
  • Translocation, Genetic / physiology

Substances

  • Calcium Channel Blockers
  • Delayed Rectifier Potassium Channels
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Ionophores
  • Kcnb1 protein, rat
  • Nitriles
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Pyrethrins
  • Shab Potassium Channels
  • Okadaic Acid
  • decamethrin
  • Calcimycin
  • Glutamic Acid
  • Potassium Chloride
  • Cyclosporine
  • Nitrendipine
  • Phosphoprotein Phosphatases
  • Cadmium Chloride
  • Potassium
  • Kainic Acid