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 language | English (US) |
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Pages (from-to) | 81-88 |
Number of pages | 8 |
Journal | Neurobiology of Disease |
Volume | 5 |
Issue number | 2 |
DOIs | |
State | Published - Aug 1998 |
Externally published | Yes |
Keywords
- Alzheimer's disease
- Apoptosis
- Calcium
- Delayed rectifier
- Ion channel
- TEA
ASJC Scopus subject areas
- Neurology