The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity

J Neurochem. 2009 Feb;108(4):909-19. doi: 10.1111/j.1471-4159.2008.05834.x. Epub 2008 Dec 10.


Chronic loss of intracellular K(+) can induce neuronal apoptosis in pathological conditions. However, the mechanism by which the K(+) channels are regulated in this process remains largely unknown. Here, we report that the increased membrane expression of Kv2.1 proteins in cortical neurons deprived of serum, a condition known to induce K(+) loss, promotes neuronal apoptosis. The increase in I(K) current density and apoptosis in the neurons deprived of serum were inhibited by a dominant negative form of Kv2.1 and MK801, an antagonist to NMDA receptors. The membrane level of Kv2.1 and its interaction with SNAP25 were increased, whereas the Kv2.1 phosphorylation was inhibited in the neurons deprived of serum. Botulinum neurotoxin, an agent known to prevent formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex, suppressed the increase in I(K) current density. Together, these results suggest that NMDA receptor-dependent Kv2.1 membrane translocation is regulated by a soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent vesicular trafficking mechanism and is responsible for neuronal cell death induced by chronic loss of K(+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Botulinum Toxins / pharmacology
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Culture Media, Serum-Free / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • N-Ethylmaleimide-Sensitive Proteins / metabolism
  • Neuromuscular Agents / pharmacology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurotoxins / metabolism*
  • Neurotoxins / pharmacology
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Deficiency / metabolism*
  • Potassium Deficiency / physiopathology
  • Protein Transport / drug effects
  • Protein Transport / physiology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Shab Potassium Channels / drug effects
  • Shab Potassium Channels / genetics
  • Shab Potassium Channels / metabolism*
  • Synaptosomal-Associated Protein 25 / metabolism
  • Transport Vesicles / metabolism


  • Culture Media, Serum-Free
  • Excitatory Amino Acid Antagonists
  • Kcnb1 protein, rat
  • Neuromuscular Agents
  • Neurotoxins
  • Receptors, N-Methyl-D-Aspartate
  • Shab Potassium Channels
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Botulinum Toxins
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, rat
  • Potassium