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Involvement of nicotinic acetylcholine receptors in amyloid β-fragmentinduced intracellular Ca2+ elevation in cultured rat cortical neurons

WU Mei-Na, LI Xin-Yi, GUO Fen, QI Jin-Shun

Department of Neurobiology； Department of Neurology, the First Hospital, Shanxi Medical University, Taiyuan 030001, China

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 Ca2+ 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 ([Ca2+]i). In the present study, we observed the effects of Aβ fragments 25-35 (Aβ25-35) and 31-35 (Aβ31-35) on [Ca2+]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 Aβ25-35 and Aβ31-35 induced similar and significant [Ca2+]i elevation in a concentrationdependent manner, and no statistical difference was found between the effects of both peptides; (2) The reverse peptide of Aβ31-35, i.e. Aβ35-31, had no effect on [Ca2+]i elevation; (3) Mecamylamine (MCA), a non-specific nAChRs antagonist, significantly and dosedependently blocked the [Ca2+]i elevation induced by Aβ25-35 or Aβ31-35; (4) Dihydro-β-erythroidine (D-β-E), a specific α4β2 subtype nAChRs antagonist, also significantly inhibited the [Ca2+]i elevation induced by Aβ25-35 and Aβ31-35, but the effect was weaker than the effect of MCA at the same concentration. These results indicate that Aβ31-35 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 [Ca2+]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.

Key words: nicotinic acetylcholine receptors; amyloid β-protein; cortical neurons; intracellular calcium concentration

Received: 2009-09-29　　Accepted: 2009-11-16

Corresponding author: 祁金顺　　E-mail: jinshunqi2006@yahoo.com

Citing This Article：

WU Mei-Na, LI Xin-Yi, GUO Fen, QI Jin-Shun. Involvement of nicotinic acetylcholine receptors in amyloid β-fragmentinduced intracellular Ca2+ elevation in cultured rat cortical neurons. Acta Physiol Sin 2009; 61 (6): 517-525 (in Chinese with English abstract).