Tan Shuhui, Ma Guozhao, Li Yanju, Li Jingxin, Yao Wei, Ren Xiaoyan, Liu Xin, Gao Jianxin
Department of Neurology, Provincial Hospital affiliated to Shandong University, Jinan, China.
Neurol Res. 2012 Sep;34(7):707-13. doi: 10.1179/1743132812Y.0000000069.
This study mainly determined the effect of beta-amyloid peptides (Abeta(1-42)) on the ATP-sensitive potassium (K(ATP)) channels of the cultured cortical and hippocampal cholinergic neurons, and further confirmed the protective effect of Diazoxide, which was the specific opener of K(ATP) channels, to the neurons.
The primary rat cortical and hippocampal cholinergic neurons were cultured. Membrane currents were measured using whole-cell patch-clamp technique.
The data showed that the outward current of neurons significantly decreased after using Abeta(1-42) (P<0·05), and that the outward current of decreased did not change after given Diazoxide again (P>0·05) compared with control. However, after being pretreated with Diazoxide for 1 hour before using Abeta(1-42), this phenomenon did not exist; that is, the membrane current of the neurons did not change when we give Abeta(1-42) after pretreatment with Diazoxide (P>0·05).
It is concluded that Abeta(1-42) inhibits the openings of the K(ATP) channels, while this inhibitory action can be removed by pretreatment with Diazoxide. It is indicated that the opening of K(ATP) channels may play a potential neuroprotective role in antineurotoxicity of Abeta(1-42), and the application of Diazoxide in small dose may be helpful in the treatment of Abeta(1-42) neurotoxicity.
本研究主要测定β-淀粉样肽（Abeta(1-42)）对培养的皮层和海马胆碱能神经元的ATP敏感性钾（K(ATP)）通道的影响，并进一步证实K(ATP)通道特异性开放剂二氮嗪对神经元的保护作用。
培养原代大鼠皮层和海马胆碱能神经元。采用全细胞膜片钳技术测量膜电流。
数据显示，使用Abeta(1-42)后神经元外向电流显著降低（P<0.05），再次给予二氮嗪后降低的外向电流与对照组相比无变化（P>0.05）。然而，在使用Abeta(1-42)前用二氮嗪预处理1小时后，这种现象不存在；即在用二氮嗪预处理后给予Abeta(1-42)时神经元膜电流无变化（P>0.05）。
得出结论，Abeta(1-42)抑制K(ATP)通道开放，而这种抑制作用可通过二氮嗪预处理消除。表明K(ATP)通道开放可能在Abeta(1-42)抗神经毒性中发挥潜在的神经保护作用，小剂量应用二氮嗪可能有助于治疗Abeta(1-42)神经毒性。
