ATP敏感性钾通道与帕金森病关系的研究进展

Advances in the association of ATP-sensitive potassium channels and Parkinson's disease

ATP敏感性钾通道(ATP-sensitive potassium channels,KATP)是一种在人体多种组织广泛分布的内向整流钾通道。KATP主要受到细胞内ATP水平、氧化应激等因素的调控,能够将细胞能量代谢和电活动相耦联,在生理和病理生理过程中发挥作用。在脑内,KATP广泛分布在黑质、海马、大脑皮质、迷走神经背侧核等区域的神经细胞内,参与神经元的兴奋性、线粒体功能以及神经递质释放等过程调节。近年来,越来越多的研究表明,KATP在帕金森病(Parkinson’s disease,PD)中发挥重要的作用。本文从KATP在黑质多巴胺能神经元退行性变中的作用,对线粒体功能和神经元放电模式的影响以及在纹状体α-突触核蛋白分泌和小胶质细胞激活中的作用等方面,综述了KATP在PD发病中的作用。

ATP-sensitive potassium channels （KATP）, as an inward rectifying potassium channel, are widely distributed in many types of tissues. KATP are activated by the depletion of ATP level and the increase in oxidative stress in ceils. The activity of KATP Couples cell metabolism with electrical activity and results in membrane hyperpolarization. KATP are ubiquitously distributed in the brain, including substantia nigra, hippocampus, hypothalamus, cerebral cortex, dorsal nucleus of vagus and glial cells, and participate in neuronal excitability, mitochondria homeostasis and neurotransmitter release. Accumulating lines of evidence suggest that KArp are the major contributing factors in the pathogenesis of Parkinson＇s disease （PD）. This review discussed the association of KATP with the pathogenic processes of PD by focusing on the roles of KATP on the degeneration of dopaminergic neurons, the functions of mitochondria, the firing pattern of dopaminergic neurons in the substantia nigra, the α-synuclein secretion from striatum, and the microglia activation.