title: Amyloid β-protein suppressed nicotinic acetylcholine receptor-mediated currents in acutely isolated rat hippocampal CA1 pyramidal neurons.
abstract: Amyloid β protein (Aβ) is responsible for the deficits of learning and memory in Alzheimer's disease (AD). The high affinity between Aβ and nicotinic acetylcholine receptors (nAChRs) suggests that the impairment of cognitive function in AD might be involved in the Aβ-induced damage of nAChRs. This study investigated the effects of Aβ fragments on nAChR-mediated membrane currents in acutely isolated rat hippocampal pyramidal neurons by using whole-cell patch clamp technique. The results showed that: (1) nonspecific nAChR agonist nicotine, selective α7 nAChR agonist choline, and α4β2 nAChR agonist epibatidine all effectively evoked inward currents in CA1 neurons at normal resting membrane potential, with different desensitization characteristics; (2) acute application of different concentrations (pM-μM) of Aβ25-35, Aβ31-35, or Aβ35-31 alone did not trigger any membrane current, but pretreatment with 1 μM Aβ25-35 and Aβ31-35 similarly and reversibly suppressed the nicotine-induced currents; (3) further, choline- and epibatidine-induced currents were also reversibly suppressed by the Aβ pretreatment, but more prominent for the choline-induced response. These results demonstrate that the functional activity of both α7 and α4β2 nAChRs in the membrane of acutely isolated hippocampal neurons was significantly downregulated by Aβ treatment, suggesting that nAChRs, especially α7 nAChRs, in the brain may be the important biological targets of neurotoxic Aβ in AD. In addition, the similar suppression of nAChR currents by Aβ25-35 and Aβ31-35 suggests that the sequence 31-35 in Aβ molecule may be a shorter active center responsible for the neurotoxicity of Aβ in AD.
authors.affiliation: Department of Radiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, People's Republic of China.
authors.forename: Ye-Xin
authors.initials: YX
authors.lastname: He
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D002794:Choline / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D009538:Nicotine; C082748:epibatidine; D002794:Choline