Journal article
Amyloid beta-peptide (AβP) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells
Brain research, Vol.643(1), pp.324-327
04/18/1994
DOI: 10.1016/0006-8993(94)90041-8
PMID: 7518331
Abstract
The neurodegenerative pathology observed in Alzheimer's Disease (AD) has been partially attributed to the neurotoxic effects of the amyloid beta-peptide (AβP), although the mechanisms underlying this neurotoxicity are unknown. Since AβP is capable of forming cation channels in lipid bilayers, it is possible that the neurotoxic effects on neurons may be mediated by a cation flux. We have used patch-clamp recording techniques to study the effects of AβP on cation currents in differentiated mouse N1E-115 neuroblastoma cells. In whole-cell recordings, incubation of cells with AβP for 24 h significantly increased the median peak inward current from −201.8 pA to −352.0 pA, and shifted the voltage at peak current (
V
peak) and that of current activation (
V
act) towards more positive potentials. For untreated cells, median
V
peak was 1.7 mV and
V
act was −28.9 mV, vs. 10.5 mV and −24.7 mV in AβP-treated cells. Incubation with the reverse sequence AβP(40-1) or AβP(25–35) did not produce significant changes in the amplitude or kinetic behavior of the inward current. At the single channel level, AβP added to the pipette increased the open probability of cation-conducting ion channels. As determined by cell viability counts, both AβP(1–40) and the AβP(25–35) fragment had neurotoxic effects; within 24 h, addition of AβP reduced the number of viable cells by more than 50%. It is suggested that the neurotoxic effects of AβP may be mediated by its ability to form cation channels de novo and/or alter the activity of cation channels already present in the cell membrane.
Details
- Title: Subtitle
- Amyloid beta-peptide (AβP) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells
- Creators
- Robert M. Davidson - University of Connecticut Health CenterLydia Shajenko - University of Connecticut Health CenterTheodore S. Donta - University of Connecticut Health Center
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.643(1), pp.324-327
- Publisher
- Elsevier B.V
- DOI
- 10.1016/0006-8993(94)90041-8
- PMID
- 7518331
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Language
- English
- Date published
- 04/18/1994
- Academic Unit
- Radiology
- Record Identifier
- 9984697725702771
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