Present address: Centre de Recherches sur la Cognition Animale, Université Paul Sabatier, UFR SVT, 118 Route de Narbonne, 31062 Toulouse, France.
Subtype-specific actions of β-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (α7, α4β2, α3β4) expressed in Xenopus laevis oocytes
Version of Record online: 29 JAN 2009
2005 British Pharmacological Society
British Journal of Pharmacology
Volume 146, Issue 7, pages 964–971, December 2005
How to Cite
Pym, L., Kemp, M., Raymond-Delpech, V., Buckingham, S., Boyd, C. A. R. and Sattelle, D. (2005), Subtype-specific actions of β-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (α7, α4β2, α3β4) expressed in Xenopus laevis oocytes. British Journal of Pharmacology, 146: 964–971. doi: 10.1038/sj.bjp.0706403
- Issue online: 29 JAN 2009
- Version of Record online: 29 JAN 2009
- (Received July 11, 2005, Revised August 17, 2005, Accepted August 22, 2005)
- Alzheimer's disease;
- β-amyloid peptides;
- nicotinic acetylcholine receptors;
- Xenopus laevis oocytes;
- two-electrode voltage-clamp
Two-electrode voltage-clamp electrophysiology has been used to study the actions of two amyloid peptides (Aβ1–42, Aβ1–40) on α7, α4β2 and α3β4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes.
The application of Aβ1–42 or Aβ1–40 (1 pM–100 nM) for 5 s does not directly activate expressed human α7, α4β2 or α3β4 nicotinic AChRs.
Aβ1–42 and Aβ1–40 are antagonists of α7 nicotinic AChRs. For example, 10 nM Aβ1–42 and Aβ1–40 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.
Aβ1–42 and Aβ1–40 (10 nM) enhance currents recorded in response to ACh (3 mM) from oocytes expressing α4β2 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 Aβ1–42. We observe an enhancement of 157±22% of control ACh-evoked current amplitude in response to 100 nM Aβ1–42 recorded from oocytes expressing α4β2 nicotinic AChRs.
Aβ1–42 and Aβ1–40 (10 nM) were without antagonist actions on the responses of α3β4 nicotinic AChRs to ACh (1 nM–3 mM).
British Journal of Pharmacology (2005) 146, 964–971. doi:10.1038/sj.bjp.0706403