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PMID: 8770205 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Beta-amyloid peptide blocks the fast-inactivating K+ current in rat hippocampal neurons.

Biophysical journal ·Vol. 70 ·No. 1 ·1996-01-00 ·Pages 296-304

Good TA, Smith DO, Murphy RM

Abstract

Deposition of beta-amyloid peptide (A beta) in senile plaques is a hallmark of Alzheimer disease neuropathology. Chronic exposure of neuronal cultures to synthetic A beta is directly toxic, or enhances neuronal susceptibility to excitotoxins. Exposure to A beta may cause a loss of cellular calcium homeostasis, but the mechanism by which this occurs is uncertain. In this work, the acute response of rat hippocampal neurons to applications of synthetic A beta was measured using whole-cell voltage-clamp techniques. Pulse application of A beta caused a reversible voltage-dependent decrease in membrane conductance. A beta selectively blocked the voltage-gated fast-inactivating K+ current, with an estimated KI < 10 microM. A beta also blocked the delayed rectifying current, but only at the highest concentration tested. The response was independent of aggregation state or peptide length. The dynamic response of the fast-inactivating current to a voltage jump was consistent with a model whereby A beta binds reversibly to closed channels and prevents their opening. Blockage of fast-inactivating K+ channels by A beta could lead to prolonged cell depolarization, thereby increasing Ca2+ influx.

MeSH Terms
Amyloid beta-Peptides/pharmacology Animals Biophysical Phenomena Biophysics Calcium/metabolism Electric Conductivity Hippocampus/drug effects,metabolism In Vitro Techniques Ion Channel Gating Ion Transport/drug effects Kinetics Membrane Potentials Models, Neurological Neurons/drug effects,metabolism Peptide Fragments/pharmacology Potassium Channel Blockers Potassium Channels/metabolism Rats Rats, Sprague-Dawley
Chemicals
Amyloid beta-Peptides Peptide Fragments Potassium Channel Blockers Potassium Channels amyloid beta-protein (1-40) Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Good T A
Department of Chemical Engineering, University of Wisconsin, Madison 53706, USA.
Smith D O
Murphy R M
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(96)79570-X
Published
1996-01-00
Pages
296-304
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1224927
Subset
IM
Grants
PHS HHS · 5T326 M08349 · United States
External Links
PubMed source DOI: 10.1016/S0006-3495(96)79570-X PMC Full Text View journal details
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