Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice

The KCNN4 potassium‐ion channel has been reported to play an important role in regulating antigen‐induced T cell effector functions in vitro. This study presents the first evidence that a selective KCNN4 blocker, TRAM‐34, confers protection against experimental autoimmune encephalomyelitis (EAE) in the mouse model. Treatment with the KCNN4 blocker did not prevent infiltration of T cells in the spinal cord, but resulted in the reduction of both the protein and the message levels of TNF‐α and IFN‐γ as well as the message levels of several other pro‐inflammatory molecules in the spinal cord. Plasma concentrations of TRAM‐34 within a 24‐h period were between the in vitro IC50 and IC90 values for the KCNN4 channel. The effect of TRAM‐34 was reversible, as indicated by the development of clinical EAE symptoms within 48 h after withdrawal of treatment. In summary, our data support the idea that KCNN4 channels play a critical role in the immune response during the development of MOG‐induced EAE in C57BL/6 mice. See accompanying Commentary: http://dx.doi.org/10.1002/eji.200526078