Diazoxide Reverses the Enhanced Expression of K(ATP) Subunits in Cholinergic Neurons Caused by Exposure to Abeta(1-42). Neurochemical research [Neurochem Res] Journal article

The ATP-sensitive potassium channel (K(ATP)) play a crucial role in coupling metabolic energy to the cell membrane potential, beta-amyloid peptide (Abeta) neurotoxicity has been associated with cellular oxidative stress and metabolic impairment. Whether there is an interaction between K(ATP) and Abeta or not? The expression of K(ATP) subunits was to be investigated after the cultured primary rat basal forebrain cholinergic neurons being exposed to Abeta(1-42). The subunits of K(ATP): 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 Abeta(1-42) (group Abeta(1-42)), pretreatment with diazoxide and then exposure to Abeta(1-42) (group diazoxide + Abeta(1-42)), and the control (group control). The results showed that in response to the treatment with Abeta(1-42) (2 mumol/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 K(ATP) subunits expression levels after exposure to Abeta(1-42) 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 Abeta(1-42) for different time (24 and 72 h) induced differential regulation of K(ATP) subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of K(ATP) may contribute to the dysfunction of K(ATP) and membrane excitability disturbance. The effect of diazoxide on K(ATP) subunits expression may explain, in part, the resistance of diazoxide to the toxicity of Abeta(1-42).

Neurochemical research [Neurochem Res]