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

Shan Ping Yu, Z. Shadi Farhangrazi, Howard S. Ying, Chen Hsiung Yeh, Dennis W. Choi

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-amyloid peptide (Aβ)-induced neuronal death. Exposure to Aβ fragment 25-35 (20 μM) or 1-42 (20 μM) enhanced the delayed rectifier K+ current I(K), shifting its activation voltage relationship toward hyperpolarized levels and increasing maximal conductance, but did not affect the transient K+ current I(A) or charybdotoxin-sensitive BK current. Reducing I(K) by adding the channel blocker tetraethylammonium (TEA, 5 mM)or raising extracellular K+ to 25 mM attenuated Aβ-induced neuronal death, even in the presence of nifedipine or gadolinium to block associated increases in Ca2+ influx. The I(A) blocker 4-aminopyridine (4-AP, 5 mM) and the Cl- channel blocker anthracene-9-carboxylic acid (ACA, 500 μM) 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.

Original languageEnglish (US)
Pages (from-to)81-88
Number of pages8
JournalNeurobiology of Disease
Volume5
Issue number2
DOIs
StatePublished - Aug 1998

Keywords

  • Alzheimer's disease
  • Apoptosis
  • Calcium
  • Delayed rectifier
  • Ion channel
  • TEA

ASJC Scopus subject areas

  • Neurology

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