Potassium channels. the"master switch" of renal fibrosis?

Progressive renal fibrosis resulting from proliferation of interstitial fibroblasts is a hallmark of chronic kidney failure, whatever the origin. The intermediate/small-conductance Ca2+-activated K+ channel (KCa3.1) promotes mitogenesis in several cell types by altering the membrane potential, thus enabling extracellular Ca2+ entry. Grgic et al. evaluated the role of KCa3.1 in renal fibroblast proliferation, testing whether deficiency or pharmacological blockade of KCa3.1 suppressed development of renal fibrosis. Mitogens stimulated KCa3.1 in murine renal fibroblasts via a MEK-dependent mechanism, while selective blockade of KCa3.1 inhibited fibroblast proliferation by promoting G0/G1 arrest. In a classical model of renal fibrosis, mouse unilateral ureteral obstruction (UUO), robust up-regulation of KCa3.1 was detectable in affected kidneys. KCa3.1 KO mice showed reduced expression of fibrotic marker expression, less chronic tubulointerstitial damage, collagen deposition and ?-smooth muscle+ cells after UUO, with better preservation of functional renal parenchyma. The selective KCa3.1 blocker TRAM-34 similarly attenuated progression of UUO-induced renal fibrosis in wild-type mice and rats. Thus, Grgic et al. believe that KCa3.1 is involved in renal fibroblast proliferation and fibrogenesis, suggesting that KCa3.1 may serve as a therapeutic target for the prevention of fibrotic kidney disease.