Subtype‐specific actions of β ‐amyloid peptides on recombinant human neuronal nicotinic acetylcholine receptors ( α 7, α 4 β 2, α 3 β 4) expressed in Xenopus laevis oocytes

Two‐electrode voltage‐clamp electrophysiology has been used to study the actions of two amyloid peptides (A β 1–42 , A β 1–40 ) on α 7, α 4 β 2 and α 3 β 4 recombinant human neuronal nicotinic acetylcholine receptors (nicotinic AChRs), heterologously expressed in Xenopus laevis oocytes. The application of A β 1–42 or A β 1–40 (1 p M – 100 n M ) for 5 s does not directly activate expressed human α 7, α 4 β 2 or α 3 β 4 nicotinic AChRs. A β 1–42 and A β 1–40 are antagonists of α 7 nicotinic AChRs. For example, 10 n M A β 1–42 and A β 1–40 both reduced the peak amplitude of currents recorded (3 m M 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. A β 1–42 and A β 1–40 (10 n M ) enhance currents recorded in response to ACh (3 m M ) from oocytes expressing α 4 β 2 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 n M A β 1–42 . We observe an enhancement of 157±22% of control ACh‐evoked current amplitude in response to 100 n M A β 1–42 recorded from oocytes expressing α 4 β 2 nicotinic AChRs. A β 1–42 and A β 1–40 (10 n M ) were without antagonist actions on the responses of α 3 β 4 nicotinic AChRs to ACh (1 n M –3 m M ).British Journal of Pharmacology (2005) 146 , 964–971. doi: 10.1038/sj.bjp.0706403