The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice
Ye Liu, Fang-Fang Zhang, Ying Song, Ran Wang, Qi Zhang, Zhong-Shan Shen, Feifei Zhang, Dan-Ya Zhong, Xiaohui Wang, Qing Guo, Qiong‐Yao Tang, Zhe Zhang
Abstract
The role of the Slack (also known as Slo2.2, K Na 1.1, or KCNT1) channel in pain-sensing is still in debate on which kind of pain it regulates. In the present study, we found that the Slack –/– mice exhibited decreased mechanical pain threshold but normal heat and cold pain sensitivity. Subsequently, X-gal staining, in situ hybridization, and immunofluorescence staining revealed high expression of the Slack channel in Isolectin B4 positive (IB4 + ) neurons in the dorsal root ganglion (DRG) and somatostatin-positive (SOM + ) neurons in the spinal cord. Patch-clamp recordings indicated the firing frequency was increased in both small neurons in DRG and spinal SOM + neurons in the Slack –/– mice whereas no obvious slow afterhyperpolarization was observed in both WT mice and Slack –/– mice. Furthermore, we found Kcnt1 gene expression in spinal SOM + neurons in Slack –/– mice partially relieved the mechanical pain hypersensitivity of Slack –/– mice and decreased AP firing rates of the spinal SOM + neurons. Finally, deletion of the Slack channel in spinal SOM + neurons is sufficient to result in mechanical pain hypersensitivity in mice. In summary, our results suggest the important role of the Slack channel in the regulation of mechanical pain-sensing both in small neurons in DRG and SOM + neurons in the spinal dorsal horn.