AUTHOR=Noh Wonjun , Pak Sojeong , Choi Geunho , Yang Sungchil , Yang Sunggu 

TITLE=Transient Potassium Channels: Therapeutic Targets for Brain Disorders

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00265

DOI=10.3389/fncel.2019.00265

ISSN=1662-5102

ABSTRACT=<p>Transient potassium current channels (I<sub>A</sub> 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<sub>A</sub> channels in these diseases has so far been underestimated. In this review, we discuss the distribution and function of I<sub>A</sub> channels. Particularly, we posit that downregulation of I<sub>A</sub> 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<sub>A</sub> channels to counteract Ca<sup>2+</sup>-permeable channels including NMDA receptors could be harnessed to restore dendritic excitability, leading to a balanced neuronal state.</p>