Subtype-specific actions of β-amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors (α7, α4β2, α3β4) expressed in Xenopus laevis oocytes

1 Two-electrode voltage-clamp electrophysiology has been used to study the actions of two amyloid peptides (A beta(1-42), A beta(1-40)) on alpha 7, alpha 4 beta 2 and alpha 3 beta 4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes. 2 The application of A beta(1-42) or A beta(1-40) (1 pM-100 nm) for 5 s does not directly activate expressed human 0, alpha 4 beta 2 or alpha 3 beta 4 nicotinic AChRs. 3 A beta(1-42) and A beta(1-40) are antagonists of alpha 7 nicotinic AChRs. For example, 10 nM A beta(1-42) and A beta(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. 4 A beta(1-42) and A beta(1-40) (10 nM) enhance currents recorded in response to ACh (3 mM) from oocytes expressing alpha 4 beta 2 nicotinic AChRs by 195 +/- 40 and 195 +/- 41% respectively. This effect is transient, reaching a peak after 3min and returning to control values after a 24min application of 10 nm A beta(1-42) . We observe an enhancement of 157 +/- 22% of control ACh-evoked current amplitude in response to 100 nm A beta(1-42) recorded from oocytes expressing alpha 4 beta 2 nicotinic AChRs. 5 A beta(1-42) and A beta(1-40) (10 nm) were without antagonist actions on the responses of alpha 3 beta 4 nicotinic AChRs to ACh (1 nM-3 mm).