β-amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes

Kelly Dineley, Karen A. Bell, Duy Bui, J. David Sweatt

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

The α7 nicotinic acetylcholine receptor is highly expressed in hippocampus and in cholinergic projection neurons from the basal forebrain, structures that are particularly vulnerable to the ravages of Alzheimer's disease. Previous work suggests that β-amyloid peptide can interact with α7 nicotinic acetylcholine receptors, although the nature of this interaction has not been well characterized. To test whether β-amyloid peptide can activate α7 nicotinic acetylcholine receptors, we expressed these receptors in Xenopus oocytes and performed two-electrode voltage clamp recordings, characterizing the response to β-amyloid peptide 1-42 applied at concentrations ranging from 1 pM to 100 nM. In α7-expressing oocytes, β-amyloid peptide 1-42 elicits inward currents at low concentrations (1-100 pM), whereas at higher concentrations (nM), less effective receptor activation is observed, indicative of receptor desensitization. Preincubation with the α7-selective agents, the antagonist methyllycaconatine, and the agonist 4-OH-GTS-21 blocked β-amyloid peptide-induced receptor activation. β-amyloid peptide 1-42 at low concentrations was able to activate the L250T mutant α7 receptor. The endogenous Ca2+-activated chloride current in Xenopus oocytes is recruited upon receptor activation since replacing Ca2+ with Ba2+ in the recording solution reduced current amplitude. Thus, when β-amyloid peptide activation of α7 receptors occurs, these currents are comprised, at least in part, of Ca2+.

Original languageEnglish (US)
Pages (from-to)25056-25061
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number28
DOIs
StatePublished - Jul 12 2002
Externally publishedYes

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Nicotinic Receptors
Xenopus
Amyloid
Oocytes
Peptides
Chemical activation
Cholinergic Neurons
Peptide Receptors
Clamping devices
Cholinergic Agents
Neurons
Chlorides
Hippocampus
Alzheimer Disease
Electrodes
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

β-amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. / Dineley, Kelly; Bell, Karen A.; Bui, Duy; Sweatt, J. David.

In: Journal of Biological Chemistry, Vol. 277, No. 28, 12.07.2002, p. 25056-25061.

Research output: Contribution to journalArticle

Dineley, Kelly ; Bell, Karen A. ; Bui, Duy ; Sweatt, J. David. / β-amyloid peptide activates α7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 28. pp. 25056-25061.
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