Noh Wonjun, Pak Sojeong, Choi Geunho, Yang Sungchil, Yang Sunggu
Department of Nano-Bioengineering, Incheon National University, Incheon, South Korea.
Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Front Cell Neurosci. 2019 Jun 13;13:265. doi: 10.3389/fncel.2019.00265. eCollection 2019.
Transient potassium current channels (I channels), which are expressed in most brain areas, have a central role in modulating feedforward and feedback inhibition along the dendroaxonic axis. Loss of the modulatory channels is tightly associated with a number of brain diseases such as Alzheimer's disease, epilepsy, fragile X syndrome (FXS), Parkinson's disease, chronic pain, tinnitus, and ataxia. However, the functional significance of I channels in these diseases has so far been underestimated. In this review, we discuss the distribution and function of I channels. Particularly, we posit that downregulation of I channels results in neuronal (mostly dendritic) hyperexcitability accompanied by the imbalanced excitation and inhibition ratio in the brain's networks, eventually causing the brain diseases. Finally, we propose a potential therapeutic target: the enhanced action of I channels to counteract Ca-permeable channels including NMDA receptors could be harnessed to restore dendritic excitability, leading to a balanced neuronal state.
瞬时钾电流通道（I 通道）在大多数脑区均有表达，在沿树突轴突轴调节前馈和反馈抑制方面发挥着核心作用。这些调节性通道的缺失与多种脑部疾病密切相关，如阿尔茨海默病、癫痫、脆性 X 综合征（FXS）、帕金森病、慢性疼痛、耳鸣和共济失调。然而，I 通道在这些疾病中的功能意义迄今一直被低估。在本综述中，我们讨论了 I 通道的分布和功能。特别是，我们认为 I 通道的下调会导致神经元（主要是树突）过度兴奋，并伴有脑网络中兴奋与抑制比例失衡，最终引发脑部疾病。最后，我们提出一个潜在的治疗靶点：增强 I 通道的作用以对抗包括 NMDA 受体在内的钙通透性通道，可用于恢复树突兴奋性，从而实现神经元状态的平衡。
