K_Ca3.1 channels modulate the processing of noxious chemical stimuli in mice

Intermediate conductance calcium-activated potassium channels (K_Ca3.1) have been recently implicated in pain processing. However, the functional role and localization of K_Ca3.1 in the nociceptive system are largely unknown. We here characterized the behavior of mice lacking K_Ca3.1 (K_Ca3.1^-/-) in various pain models and analyzed the expression pattern of K_Ca3.1 in dorsal root ganglia (DRG) and the spinal cord. K_Ca3.1^-/- mice demonstrated normal behavioral responses in models of acute nociceptive, persistent inflammatory, and persistent neuropathic pain. However, their behavioral responses to noxious chemical stimuli such as formalin and capsaicin were increased. Accordingly, formalin-induced nociceptive behavior was increased in wild-type mice after administration of the K_Ca3.1 inhibitor TRAM-34. In situ hybridization experiments detected K_Ca3.1 in most DRG satellite glial cells, in a minority of DRG neurons, and in ependymal cells lining the central canal of the spinal cord. Together, our data point to a specific inhibitory role of K_Ca3.1 for the processing of noxious chemical stimuli.