Effects Of Aβ1-42on The Current Of Katp Channels In Cultured Cholinergic Neurons

Objective:(3amyloid protein plays an important role in the course of Alzheimer’disease(AD). Increased brain accumulation of Aβ associated with energy metabolic disorders is finally leading to the death of brain neurons by apoptosis. There are mainly two forms of Aβ, which contains Aβ1-40and Aβ1-42., while the latter precipitated first and it is difficult to dissolve. Many researchers attach important to the Aβ1-42.ATP-sensitive potassium channels (KATP) is comprise octamers of four Kir6pore-forming subunits associated with four sulphonylurea receptor subunits. Their general role is to couple the membrane potassium conductance, and so membrane potential, of the cell to its metabolic state. It is reported that being exposed to AP1-42for24h, the expression of subunits Kir6.1and SUR2in the cultured neurons were increased significantly, while the changes can be completely reversed by pretreated with diazoxide. However, research of Aβ1-42to the current of KATP channels on cholinergic neurons in the level of physiology remain unclear.Methods:1primary rat cortical and hippocampal cholinergic neurons were cultured and identified using immunohistochemical methods.2the current of KATP was measured using patch clamp whole cell recordings before and after application of Aβ1-42, and then adding diazoxide to observe the changes of the current.3pretreatment with diazoxide for lh first, then adding AP1-42to the cells, using patch clamp whole cell recordings to observe the changes of the current.Result: 1compared with the controls, the outward current of neurons significantly decreased after using Aβ1-42(P<0.05); and there was no obvious change after giving diazoxide an opener of KATP channels(P>0.05).2the current of the KATP channel has no change when adding Aβ1-42to the neurons after the cells pretreated with diazoxide for1h(P>0.05)。Conclusion:1Aβ1-42lead to a significant decline in the level of the outward current of KATP channels. This phenomenon couldn’t be reversed by diazoxide.2pretreatment with diazoxide could reverse the decline of the current due to the application of Aβ1-42.Significance:It is observed that Aβ1-42could reduce the levels of the current of KATP, and this phenomenon could not be reversed by diazoxide. However, pretreatment with diazoxide could reverse the decline of the current due to the application of Aβ1-42The protection of diazoxide may play an important role in the process of maintaining the normal function of cells. Studying of KATP channels opener is conductive to further reveal the pathological mechanisms of AD, also it provides a new direction of drugs in treatment of AD.