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

Abstract

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-alpha and IFN-gamma 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 IC(50) and IC(90) 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.

• Authors: Eva-Pia Reich, Long Cui, Lily Yang, Catherine Pugliese-Sivo, Andrei Golovko, Mary Petro, Galya Vassileva, Inhou Chu, Amin A Nomeir, Li-Kang Zhang, Xian Liang, Joseph A Kozlowski, Satwant K Narula, Paul J Zavodny, Chuan-Chu Chou
• Journal: European journal of immunology (Eur J Immunol) Vol. 35 Issue 4 Pg. 1027-36 (Apr 2005) ISSN: 0014-2980 [Print] Germany
• PMID: 15770697 (Publication Type: Journal Article)

Chemical References

• Intermediate-Conductance Calcium-Activated Potassium Channels
• Kcnn4 protein, mouse
• Potassium Channels, Calcium-Activated
• RNA, Messenger

Topics

• Animals
• Cell Movement (immunology, physiology)
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, prevention & control)
• Inflammation (immunology)
• Intermediate-Conductance Calcium-Activated Potassium Channels
• Mice
• Potassium Channels, Calcium-Activated (antagonists & inhibitors)
• RNA, Messenger (metabolism)
• Spinal Cord (immunology, physiology)