Aβ(25–35) and Aβ(1–40) act on different calcium channels in CA1 hippocampal neurons

doi:10.1016/S0006-291X(02)02072-7

Biochemical and Biophysical Research Communications

Volume 296, Issue 5, 6 September 2002, Pages 1317-1321

https://doi.org/10.1016/S0006-291X(02)02072-7 Get rights and content

Abstract

The acute effects of β-amyloid (25–35) and (1–40) on high voltage activated calcium channels were compared in CA1 pyramidal cells of adult mouse hippocampal slices using the whole-cell patch-clamp recording. Bath application of oligomeric β-amyloid (25–35) reversibly increased the barium current (I_Ba) to 1.61 (normalized amplitude), while oligomeric β-amyloid (1–40) reversibly enhanced the I_Ba to 1.74. Reverse-sequence β-amyloid [(35–25) and (40–1)] had no effect. The effect of β-amyloid (25–35) was blocked by nifedipine, a selective antagonist of L-type calcium channels. In contrast, the effect of β-amyloid (1–40) was not blocked by nifedipine and I_Ba was enhanced to 4.96. It is concluded that these oligomeric peptides may act through different types of calcium channels and/or receptors. The toxicity of Aβ(25–35) implicates a potentiation of L-type calcium channels while the one of Aβ(1–40) is related to an increase of non-L-type calcium channels, which may involve an increase in transmitter release.

Section snippets

Methods

SDS–PAGE. To determine whether the Aβ peptides were oligomeric or monomeric, we performed SDS–PAGE. Aliquot of each chromatographic fraction ( $20 μl$ ) was mixed with Tris–HCl SDS sample buffer ( $10 μl$ ) and boiled for 10 min, immediately prior electrophoresis (≈1 nmol/lane was electrophoresed; [25]) on 4–20% gradient acrylamide/bi-acrylamide gel (BioRad) at 125 V for 1 h. Proteins were visualized by silver staining. Image analysis was performed using Photomat (Microvision Instrument).

Slice preparation.

Results

SDS–PAGE analysis performed on the $200 μM$ stock solution revealed that Aβ(1–40) and Aβ(25–35) were oligomeric (4–6 mers for Aβ(1–40) and 6–8 mers for Aβ(25–35). Moreover DMSO, the solvent used in the nifedipine experiments, when added to the stock solution at the concentration of $5‰$ (a dilution factor five times superior to that used in the experiment) did not change the oligomeric structure of the Aβ peptides (data not shown).

Discussion

The main finding of this paper is that adult CA1 hippocampal cells acutely exposed to nanomolar doses of Aβ peptides (25–35) or (1–40) exhibit an increase in the activity of different calcium channel types. In contrast to previous works [21], [23], [24], [27], [28], we have tested the Aβ peptides in its oligomeric form, a state of aggregation, which precedes the formation of fibrillar Aβ and plaques. An interesting issue, since the best pathological correlate of dementia is loss of synaptic

Acknowledgements

We are grateful to Dr. Ann Lohof for critical reading of the paper. This work has been supported by a grant by Fondation pour la Recherche Medicale.

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Aβ(25–35) and Aβ(1–40) act on different calcium channels in CA1 hippocampal neurons

Abstract

Section snippets

Methods

Results

Discussion

Acknowledgements

Amyloid deposition as the central event in the aetiology of Alzheimer's disease

TIPS

Normal and abnormal biology of the β-amyloid precursor protein

Annu. Rev. Neurosci.

Mass spectrometry of purified amyloid β-protein in Alzheimer's disease

J. Biol. Chem.

Differences between vascular and plaque core amyloid in Alzheimer' disease

J. Neurochem.

Amyloid β-peptide is produced by cultured cells during normal metabolism

Nature

Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids

Nature

In vitro aging of β-amyloid protein causes peptide aggregation and neurotoxicity

Brain Res.

Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachynin neuropeptides

Science

Protofibrillar intermediate induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons

J. Neurosci.

Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins

Proc. Natl. Acad. Sci. USA

Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo

Nature

The Ca2+ influx induced by β-amyloid peptide 25–35 in cultured hippocampal neurons results from network excitation

J. Neurobiol.

β-Amyloid peptides destabilized calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity

J. Neurosci.

β-Amyloid precursor protein mismetabolism and loss of calcium homeostasis in Alzheimer's disease

Ann. N. Y. Acad. Sci.

Giant multilevel cation channels formed by Alzheimer disease amyloid β-protein [AβP-(1–40)] in bilayer membranes

Proc. Natl. Acad. Sci. USA

Amyloid β protein-(1–42) forms calcium permeable, Zn2+-sensitive channel

J. Biol. Chem.

Amyloid β protein potentiates Ca2+ channels: a possible involvement of free radicals

J. Neurochem.

Diffusible, nonfibrillar ligands derived from Aβ_1–42 are potent central nervous system neurotoxins

The Ca²⁺ influx induced by β-amyloid peptide 25–35 in cultured hippocampal neurons results from network excitation

Amyloid β protein-(1–42) forms calcium permeable, Zn²⁺-sensitive channel

Amyloid β protein potentiates Ca²⁺ channels: a possible involvement of free radicals