Subtype-specific actions of beta-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (alpha7, alpha4beta2, alpha3beta4) expressed in Xenopus laevis oocytes.
Two-electrode voltage-clamp electrophysiology has been used to study the actions of two amyloid peptides (Abeta(1-42), Abeta(1-40)) on alpha7, alpha4beta2 and alpha3beta4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes. The application of Abeta(1-42) or Abeta(1-40) (1 pM-100 nM) for 5 s does not directly activate expressed human alpha7, alpha4beta2 or alpha3beta4 nicotinic AChRs.Abeta(1-42) and Abeta(1-40) are antagonists of alpha7 nicotinic AChRs. For example, 10 nM Abeta(1-42) and Abeta(1-40) both reduced the peak amplitude of currents recorded (3 mM ACh) to 48+/-5 and 45+/-10% (respectively) of control currents recorded in the absence of peptide. In both the cases the effect is sustained throughout a 30 min peptide application and is poorly reversible.Abeta(1-42) and Abeta(1-40) (10 nM) enhance currents recorded in response to ACh (3 mM) from oocytes expressing alpha4beta2 nicotinic AChRs by 195+/-40 and 195+/-41% respectively. This effect is transient, reaching a peak after 3 min and returning to control values after a 24 min application of 10 nM Abeta(1-42). We observe an enhancement of 157+/-22% of control ACh-evoked current amplitude in response to 100 nM Abeta(1-42) recorded from oocytes expressing alpha4beta2 nicotinic AChRs.Abeta(1-42) and Abeta(1-40) (10 nM) were without antagonist actions on the responses of alpha3beta4 nicotinic AChRs to ACh (1 nM-3 mM).
Pym
Luanda
L
MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Kemp
Mark
M
Raymond-Delpech
Valérie
V
Buckingham
Steven
S
Boyd
C A R
CA
Sattelle
David
D
D000109:Acetylcholine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000187:drug effects; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; C579167:Chrna7 protein, human; D007473:Ion Channels; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C403530:nicotinic receptor alpha3beta4; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine