Slack Channels Null Mice Exhibit Increased Sensitivity to Mechanical Stimuli but Normal Response to Thermal Stimuli

Abstract

Slack channels are sodium activated potassium channel that are expressed in brain, heart and dorsal root ganglia (DRG) neurons. As reported previously, they had been involved in regulating thermal pain (Huang F, et al) and neuropathic pain (Lu R. et al). In this abstract, we reported using a Slack channel KO mice line to examine the role of Slack played in pain processing. Heat plate, cold plate and Von Frey test are used to detect thermal (including cold and hot) pain and mechanical pain sensitivity of wild type and KO mice respectively. In situ hybridization, X-gal staining and immunostaining are used to detect the Slack channel expression in DRG neurons and spinal cord. Also, we use patch-clamp method to detect spontaneous and injected current induced action potential firing. Our results show KO mice demonstrate enhanced mechanical pain sensitivity but not hot and cold pain sensitivity. Slack channels are widely expressed in DRG neurons and spinal cord. In spinal cord, immune-staining results show Slack channel are not only expressed in dorsal horn but also are expressed in ventral horn. Electrophysiological recording shows small and middle DRG neurons in KO mice have more firing rate than DRG neurons in WT mice. But the firing rate in big DRG neurons of KO mice did not show statistical different firing rate with big DRG neurons of WT mice. Taken together, these results suggest Slack channels play important roles in regulating mechanical pain signal transmission.