Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels

J Neurosci. 2003 Jun 15;23(12):4798-802. doi: 10.1523/JNEUROSCI.23-12-04798.2003.

Abstract

Cellular K+ efflux is a requisite event in the unfolding of apoptosis programs across many types of cells and death-inducing stimuli; however, the molecular identities of the ion channels mediating this key event have remained undefined. Here, we show that Kv2.1-encoded K+ channels are responsible for the expression of apoptosis in cortical neurons in vitro. Transient expression of two different dominant-negative forms of this subunit in neurons completely eliminated the enhancement of K+ currents that normally accompanies the cell death process. Importantly, neurons deficient in functional Kv2.1-encoded K+ channels were protected from oxidant and staurosporine-induced apoptosis. Finally, Chinese hamster ovary cells, which do not express endogenous voltage-gated K+ channels, became substantially more sensitive to apoptosis after transient expression of wild-type Kv2.1. These results suggest that Kv2.1-encoded K+ channels are necessary for the apoptotic signaling cascade in mammalian cortical neurons in culture and are sufficient for increasing the susceptibility to apoptogens in a nonexcitable cell.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cytoprotection / genetics
  • Cytoprotection / physiology
  • Delayed Rectifier Potassium Channels
  • Genes, Dominant
  • Neurons / cytology
  • Neurons / metabolism*
  • Oxidants / toxicity
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Rats
  • Shab Potassium Channels
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Staurosporine / toxicity
  • Transfection

Substances

  • Delayed Rectifier Potassium Channels
  • Kcnb1 protein, rat
  • Oxidants
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Shab Potassium Channels
  • Staurosporine
  • Potassium