title: 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.affiliation: Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
authors.forename: Eva-Pia
authors.initials: EP
authors.lastname: Reich
authors.forename: Long
authors.initials: L
authors.lastname: Cui
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.forename: Catherine
authors.initials: C
authors.lastname: Pugliese-Sivo
authors.forename: Andrei
authors.initials: A
authors.lastname: Golovko
authors.forename: Mary
authors.initials: M
authors.lastname: Petro
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Inhou
authors.initials: I
authors.lastname: Chu
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nomeir
authors.forename: Li-Kang
authors.initials: LK
authors.lastname: Zhang
authors.forename: Xian
authors.initials: X
authors.lastname: Liang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Satwant K
authors.initials: SK
authors.lastname: Narula
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Zavodny
authors.forename: Chuan-Chu
authors.initials: CC
authors.lastname: Chou
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D007249:Inflammation / Q000276:immunology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051379:Mice; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000276:immunology / Q000502:physiology
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496925:Kcnn4 protein, mouse; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger