PDF(Pubmed)
Abstract：
The role of the Slack (also known as Slo2.2, KNa1.1, 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.
摘要：
Slack（也称为Slo2.2，KNa1.1或KCNT1）通道在疼痛感知中的作用仍在争论中，它可以调节哪种疼痛。在本研究中,我们发现Slack-/-小鼠表现出机械痛阈值降低，但热和冷疼痛敏感性正常。随后，X-gal染色,原位杂交,免疫荧光染色显示，脊髓背根神经节（DRG）中IsolectinB4阳性（IB4）神经元和生长抑素阳性（SOM）神经元中Slack通道的高表达。膜片钳记录表明，DRG的小神经元和Slack-/-小鼠的脊髓SOM神经元的放电频率均增加，而WT小鼠和Slack-/-小鼠均未观察到明显的缓慢后超极化。此外，我们发现Slack-/-小鼠脊髓SOM神经元中Kcnt1基因的表达部分减轻了Slack-/-小鼠的机械性疼痛超敏反应，并降低了脊髓SOM神经元的AP放电率。最后,脊髓SOM+神经元中松弛通道的缺失足以导致小鼠的机械性疼痛超敏反应。总之,我们的结果表明Slack通道在DRG小神经元和脊髓背角SOM+神经元的机械性疼痛感知调节中的重要作用.
