title: Diazoxide reverses the enhanced expression of KATP subunits in cholinergic neurons caused by exposure to Aβ₁₋₄₂.
abstract: The ATP-sensitive potassium channel (KATP) play a crucial role in coupling metabolic energy to the cell membrane potential, β-amyloid peptide (Aβ) neurotoxicity has been associated with cellular oxidative stress and metabolic impairment. Whether there is an interaction between KATP and Aβ or not? The expression of KATP subunits was to be investigated after the cultured primary rat basal forebrain cholinergic neurons being exposed to Aβ₁₋₄₂. The subunits of KATP: Kir6.1, Kir6.2, SUR1 and SUR2 expressing change was observed by double Immunofluorescence and immunoblotting in cultured cholinergic neurons from different groups: treatment with Aβ₁₋₄₂ (group Aβ₁₋₄₂), pretreatment with diazoxide and then exposure to Aβ₁₋₄₂ (group diazoxide + Aβ₁₋₄₂), and the control (group control). The results showed that in response to the treatment with Aβ₁₋₄₂ (2 μmol/L) for 24 h, the expression of Kir6.1 and SUR2 were significantly up-regulated, while this change can be partly reversed by pretreatment with diazoxide (1 mmol/L) for 1 h. There were significant increases in all KATP subunits expression levels after exposure to Aβ₁₋₄₂ for 72 h. However, the up-regulation of Kir6.1, Kir6.2 and SUR2 except SUR1 can be partly reversed by pretreatment with diazoxide (1 mmol/L) for 1 h. It is concluded that exposure to Aβ₁₋₄₂ for different time (24 and 72 h) induced differential regulation of KATP subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of KATP may contribute to the dysfunction of KATP and membrane excitability disturbance. The effect of diazoxide on KATP subunits expression may explain, in part, the resistance of diazoxide to the toxicity of Aβ₁₋₄₂.
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University, No. 324 Jingwu Weiqi Road, 250021 Jinan, Shandong, People's Republic of China. maguozhao@yahoo.com.cn
authors.forename: Guozhao
authors.initials: G
authors.lastname: Ma
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gao
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Fu
authors.forename: Liangliang
authors.initials: L
authors.lastname: Jiang
authors.forename: Ruixia
authors.initials: R
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kejing
authors.initials: K
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D054086:KATP Channels / Q000096:biosynthesis / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D018678:Cholinergic Agents; D054086:KATP Channels; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003981:Diazoxide