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

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

doi:10.3389/fnmol.2020.00105

Inhibition of M/K_v7 Currents Contributes to Chloroquine-Induced Itch in Mice

Front Mol Neurosci. 2020 Jun 30:13:105. doi: 10.3389/fnmol.2020.00105. eCollection 2020.

Authors

Dong Zhang^{1

2

3

4

5}, Hongchao Men^{1

2

3

4

5}, Ludi Zhang^{1

2

3

4}, Xiangxin Gao^{1

2

3

4}, Jingjing Wang^{1

2

3

4}, Leying Li^{1

2

3

4}, Qiaoying Zhu^{1

2

3

4}, Hailin Zhang^{1

2

3

4}, Zhanfeng Jia^{1

2

3

4}

Affiliations

¹ Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
² Center for Innovative Drug Research and Evaluation, Institute of Medical Science and Health, Hebei Medical University, Shijiazhuang, China.
³ The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, China.
⁴ The Key Laboratory of New Drug Pharmacology and Toxicology, Shijiazhuang, China.
⁵ Department of Anesthesiology, Hebei General Hospital, Shijiazhuang, China.

Abstract

M/K_v7 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_v7 channel activity contributes to generation of itch in mice. CQ enhances excitability of the primary sensory neurons through inhibiting M/K_v7 potassium currents in a Ca²⁺ influx-dependent manner. Specific M/K_v7 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.

Keywords: M/Kv7 potassium currents; chloroquine; dorsal root ganglion neurons; inhibition; itch.