Enhancement of outward potassium current may participate in beta-amyloid peptide-induced cortical neuronal death

Neurobiol Dis. 1998 Aug;5(2):81-8. doi: 10.1006/nbdi.1998.0186.


In light of recent evidence implicating the upregulation of outward K+ current in mediating several forms of neuronal apoptosis, we tested the hypothesis that such an upregulation might specifically contribute to the pathogenesis of beta-amyloid peptide (A beta)-induced neuronal death. Exposure to A beta fragment 25-35 (20 microM) or 1-42 (20 microM) enhanced the delayed rectifier K+ current IK, shifting its activation voltage relationship toward hyperpolarized levels and increasing maximal conductance, but did not affect the transient K+ current IA or charybdotoxin-sensitive BK current. Reducing IK by adding the channel blocker tetraethylammonium (TEA, 5 mM) or raising extracellular K+ to 25 mM attenuated A beta-induced neuronal death, even in the presence of nifedipine or gadolinium to block associated increases in Ca2+ influx. The IA blocker 4-aminopyridine (4-AP, 5 mM) and the CI- channel blocker anthracene-9-carboxylic acid (ACA, 500 microM) were not neuroprotective. These data raise the intriguing possibility that manipulations aimed at reducing outward K+ current may provide an approach to reducing neuronal degeneration in patients with Alzheimer's disease.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cell Death / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Coculture Techniques
  • Delayed Rectifier Potassium Channels
  • Fetus
  • Mice
  • Neuroglia
  • Neurons / drug effects
  • Neurons / physiology*
  • Peptide Fragments / pharmacology*
  • Potassium / physiology
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Quaternary Ammonium Compounds / pharmacology


  • Amyloid beta-Peptides
  • Delayed Rectifier Potassium Channels
  • Peptide Fragments
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Quaternary Ammonium Compounds
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (25-35)
  • tetramethylammonium
  • Potassium