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

Sumon Pal, Karen A. Hartnett, Jeanne M. Nerbonne, Edwin S. Levitan, Elias Aizenman

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

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.

Original languageEnglish
Pages (from-to)4798-4802
Number of pages5
JournalJournal of Neuroscience
Volume23
Issue number12
DOIs
StatePublished - Jun 15 2003

Keywords

  • Apoptosis
  • Chinese hamster ovary
  • Cortical neurons
  • Kv2.1
  • Luciferase
  • Neurotoxicity
  • Potassium channels
  • Transfection

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