Involvement of nicotinic acetylcholine receptors in amyloid β-fragment-induced intracellular Ca(2+) elevation in cultured rat cortical neurons.
- Author:
Mei-Na WU
1
;
Xin-Yi LI
;
Fen GUO
;
Jin-Shun QI
Author Information
1. Department of Neurobiology, the First Hospital, Shanxi Medical University, Taiyuan 030001, China.
- Publication Type:Journal Article
- MeSH:
Amyloid beta-Peptides;
chemistry;
Animals;
Calcium;
metabolism;
Cells, Cultured;
Neurons;
metabolism;
Peptide Fragments;
chemistry;
Rats;
Receptors, Nicotinic;
metabolism
- From:
Acta Physiologica Sinica
2009;61(6):517-525
- CountryChina
- Language:English
-
Abstract:
The amyloid β-protein (Aβ)-induced disturbance of intracellular calcium homeostasis has been regarded as the final route whereby Aβ insults neurons. However, the mechanism of Aβ-induced Ca(2+) overloading is still unclear so far. Especially, it remains to be clarified whether nicotinic acetylcholine receptors (nAChRs) are involved in the Aβ-induced elevation of intracellular calcium concentration ([Ca(2+)](i)). In the present study, we observed the effects of Aβ fragments 25-35 (Aβ(25-35)) and 31-35 (Aβ(31-35)) on [Ca(2+)](i) in primary cultured rat cortical neurons using laser-scanning confocal calcium imaging technique, and investigated its probable cholinergic mechanism. The results showed that: (1) Both Aβ(25-35) and Aβ(31-35) induced similar and significant [Ca(2+)](i) elevation in a concentration-dependent manner, and no statistical difference was found between the effects of both peptides; (2) The reverse peptide of Aβ(31-35), i.e. Aβ(35-31), had no effect on [Ca(2+)](i) elevation; (3) Mecamylamine (MCA), a non-specific nAChRs antagonist, significantly and dose-dependently blocked the [Ca(2+)](i) elevation induced by Aβ(25-35) or Aβ(31-35) (4) Dihydro-β-erythroidine (D-β-E), a specific α4β2 subtype nAChRs antagonist, also significantly inhibited the [Ca(2+)](i) elevation induced by Aβ(25-35) and Aβ(31-35), but the effect was weaker than the effect of MCA at the same concentration. These results indicate that Aβ(31-35) may be a shorter active sequence in full length of Aβ molecule, and the overactivation of nAChRs, including α4β2 subtype, may be, at least partly, responsible for the Aβ-induced elevation of [Ca(2+)](i) in cultured rat cortical neurons. Thus, the present study suggests a new potential target of Aβ in the brain, and provides a new insight into the mechanisms by which Aβ impairs the cognitive function in Alzheimer's disease.
