Effects of A beta sub(1-42) on the Subunits of K sub(ATP) Expression in Cultured Primary Rat Basal Forebrain Neurons

ATP-sensitive potassium channels (K sub(ATP)) play a crucial role in coupling metabolic energy to the membrane potential of cells, thereby functioning as cellular 'metabolic sensors.' Recent evidence has showed a connection between the amyloid neurotoxic cascade and metabolic impairment. With regard to their neuroprotection in other neuronal preparations, K sub(ATP) channels may mediate a potential neuroprotective role in Alzheimer's disease (AD). To investigate the effects of A beta sub(1-42) on the subunits of K sub(ATP) expression in cultured primary rat basal forebrain cholinergic neurons, primary rat basal forebrain neurons were cultured and evaluated. The subunits of K sub(ATP): Kir6.1, Kir6.2, SUR1 and SUR2 expressing changes were observed by double immunofluorescence and immunoblotting when the neurons were exposed to A beta sub(1-42)(2 mu M) for different time (0, 24, 72 h). We found a significant increase in the expression of Kir6.1 and SUR2 in the cultured neurons being exposed to A beta sub(1-42) for 24 h, while Kir6.2 and SUR1 showed no significant change. However, after being treated with A beta sub(1-42) for 72 h, the expression of the four subunits was all increased significantly compared with the control. These findings suggest that being exposed to A beta sub(1-42 )for different time (24 and 72 h) induces differential regulations of K sub(ATP) subunits expression in cultured primary rat basal forebrain cholinergic neurons. The change in composition of K sub(ATP) may contribute to resist the toxicity of A beta sub(1-42.)