Referenced in: none

Automatically associated channels: Kv1.3

Title: Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis.

Authors: Toshitake Hyodo, Takashi Oda, Yuichi Kikuchi, Keishi Higashi, Taketoshi Kushiyama, Kojiro Yamamoto, Muneharu Yamada, Shigenobu Suzuki, Ryota Hokari, Manabu Kinoshita, Shuhji Seki, Hidehiko Fujinaka, Tadashi Yamamoto, Soichiro Miura, Hiroo Kumagai

Journal, date & volume: Am. J. Physiol. Renal Physiol., 2010 Dec , 299, F1258-69

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20810612

Abstract
The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (T(EM)) without affecting the function of naïve T cells (T(N)) and central memory T cells (T(CM)). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4(+) T cells and some of the CD8(+) T cells had the T(EM) phenotype (CD45RC(-)CD62L(-)). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that T(EM) and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.