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Enhancement of Outward Potassium Current May Participate in β-Amyloid Peptide-Induced Cortical Neuronal Death

https://doi.org/10.1006/nbdi.1998.0186Get rights and content

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+currentIK, shifting its activation voltage relationship toward hyperpolarized levels and increasing maximal conductance, but did not affect the transient K+currentIAor charybdotoxin-sensitive BK current. ReducingIKby 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. TheIAblocker 4-aminopyridine (4-AP, 5 mM) and the Clchannel 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.

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  • Cited by (0)

    C. A. TysonJ. M. Frazier

    1

    To whom correspondence should be addressed at Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110. Fax: 314-362-1771.E-mail: [email protected].

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