beta -Amyloid peptide activates alpha 7 nicotinic acetylcholine receptors expressed in Xenopus oocytes.
The alpha7 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 beta-amyloid peptide can interact with alpha7 nicotinic acetylcholine receptors, although the nature of this interaction has not been well characterized. To test whether beta-amyloid peptide can activate alpha7 nicotinic acetylcholine receptors, we expressed these receptors in Xenopus oocytes and performed two-electrode voltage clamp recordings, characterizing the response to beta-amyloid peptide 1-42 applied at concentrations ranging from 1 pm to 100 nm. In alpha7-expressing oocytes, beta-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 alpha7-selective agents, the antagonist methyllycaconatine, and the agonist 4-OH-GTS-21 blocked beta-amyloid peptide-induced receptor activation. beta-amyloid peptide 1-42 at low concentrations was able to activate the L250T mutant alpha7 receptor. The endogenous Ca(2+)-activated chloride current in Xenopus oocytes is recruited upon receptor activation since replacing Ca(2+) with Ba(2+) in the recording solution reduced current amplitude. Thus, when beta-amyloid peptide activation of alpha7 receptors occurs, these currents are comprised, at least in part, of Ca(2+).
Dineley
Kelly T
KT
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA. kdineley@cns.bcm.tmc.edu
Bell
Karen A
KA
Bui
Duy
D
Sweatt
J David
JD
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015640:Ion Channel Gating; D017136:Ion Transport; D008564:Membrane Potentials; D009865:Oocytes / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014982:Xenopus laevis
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C075222:amyloid beta-protein (1-42); D002118:Calcium