Amyloid betapeptide decreases alpha7 receptor potentiation

LASALA, MATÍAS; FABIANI, C.; URANGA R; ANTOLLINI, S.; CORRADI J; BOUZAT C

Congreso; Congreso Conjunto de sociedades de Biociencia; 2017

Amyloid β peptide (Aβ) is a key player in the development of Alzheimer disease (AD). Aβ is visible as the primary component of senile plaques in the brains of Alzheimer?s patients. Cholinergic activity mediated by human α7 nicotinic receptors is decreased in AD, and potentiation of α7 by positive allosteric modulators (PAMs) is emerging as a novel therapeutic strategy for improving memory and cognition. There are reports showing functional interaction of Aβ with α7, but the reported effects are very varied and the underlying mechanisms are not clear. Here we explored the effect of Aβ1-40 and Aβ1-42 on human α7 at the patch-clamp single-channel level. α7 channel activity elicited by 100 µM ACh consists of brief and isolated openings. In the presence of PAMs, open channel lifetime is increased and openings appear grouped in long activation episodes. The type II PAM PNU-120596 (1 µM) prolongs open durations and elicits activation episodes of 2 s. In the presence of Aβ there is a statistically significant decrease in the mean duration of the potentiated activation episodes, which is 2.6-fold at 100 nM Aβ1-40 (p