Liu Ye, Zhang Fang-Fang, Song Ying, Wang Ran, Zhang Qi, Shen Zhong-Shan, Zhang Fei-Fei, Zhong Dan-Ya, Wang Xiao-Hui, Guo Qing, Tang Qiong-Yao, Zhang Zhe
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China.
Front Mol Neurosci. 2022 Mar 11;15:811441. doi: 10.3389/fnmol.2022.811441. eCollection 2022.
The role of the Slack (also known as Slo2.2, K1.1, 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, 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 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.
Slack通道（也称为Slo2.2、K1.1或KCNT1）在痛觉感知中的作用仍存在争议，即它调节哪种类型的疼痛。在本研究中，我们发现Slack基因敲除小鼠的机械性疼痛阈值降低，但热痛和冷痛敏感性正常。随后，X-gal染色、杂交和免疫荧光染色显示，背根神经节（DRG）中Isolectin B4阳性（IB4）神经元和脊髓中生长抑素阳性（SOM）神经元中Slack通道高表达。膜片钳记录表明，Slack基因敲除小鼠的DRG中小神经元和脊髓SOM神经元的放电频率均增加，而野生型小鼠和Slack基因敲除小鼠均未观察到明显的慢后超极化。此外，我们发现Slack基因敲除小鼠脊髓SOM神经元中的基因表达部分缓解了Slack基因敲除小鼠的机械性疼痛超敏反应，并降低了脊髓SOM神经元的动作电位发放率。最后，脊髓SOM神经元中Slack通道的缺失足以导致小鼠出现机械性疼痛超敏反应。总之，我们的结果表明Slack通道在DRG中小神经元和脊髓背角SOM神经元的机械性痛觉调节中起重要作用。
