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

摘要

class="enumerated" style="list-style-type:decimal">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).