AUTHOR=Zhang Dong , Men Hongchao , Zhang Ludi , Gao Xiangxin , Wang Jingjing , Li Leying , Zhu Qiaoying , Zhang Hailin , Jia Zhanfeng 

TITLE=Inhibition of M/Kv7 Currents Contributes to Chloroquine-Induced Itch in Mice

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=13

YEAR=2020

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2020.00105

DOI=10.3389/fnmol.2020.00105

ISSN=1662-5099

ABSTRACT=<p>M/K<sub>v</sub>7 potassium channels play a key role in regulation of neuronal excitability. Modulation of neuronal excitability of primary sensory neurons determines the itch sensation induced by a variety of itch-causing substances including chloroquine (CQ). In the present study, we demonstrate that suppression of M/K<sub>v</sub>7 channel activity contributes to generation of itch in mice. CQ enhances excitability of the primary sensory neurons through inhibiting M/K<sub>v</sub>7 potassium currents in a Ca<sup>2+</sup> influx-dependent manner. Specific M/K<sub>v</sub>7 channel opener retigabine (RTG) or tannic acid (TA) not only reverses the CQ-induced enhancement of neuronal excitability but also suppresses the CQ-induced itch behavior. Systemic application of RTG or TA also significantly inhibits the itch behavior induced by a variety of pruritogens. Taken together, our findings provide novel insight into the molecular basis of CQ-induced itch sensation in mammals that can be applied to the development of strategies to mitigate itch behavior.</p>