Referenced in: none

Automatically associated channels: Kir6.1 , Kir6.2

Title: Diazoxide reverses the enhanced expression of KATP subunits in cholinergic neurons caused by exposure to Aβ₁₋₄₂.

Authors: Guozhao Ma, Jianxin Gao, Qingxi Fu, Liangliang Jiang, Ruixia Wang, Yong Zhang, Kejing Liu

Journal, date & volume: Neurochem. Res., 2009 Dec , 34, 2133-40

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19488853

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.