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The beta-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6 Lu P; Boros S; Chang Q; Bindels RJ; Hoenderop JGNephrol Dial Transplant 2008[Nov]; 23 (11): 3397-402BACKGROUND: Active Ca(2+) reabsorption in the kidney is facilitated by the epithelial transient receptor potential vanilloid Ca(2+) channel subtype 5 (TRPV5). The complex-glycosylated TRPV5 is expressed at the apical membrane of the renal distal convoluted tubule (DCT) cells where the pro-urine hormone klotho can stimulate its activity by N-oligosaccharide hydrolysis. This study investigates whether klotho and its closely related analogue, beta-glucuronidase, can activate other renal ion channels than TRPV5 expressed by DCT cells. METHODS: To determine the specificity of this stimulatory effect of klotho and beta-glucuronidase, a selection of ion channels and transporters expressed in the kidney (TRPV4, TRPV5, TRPV6 and TRPM6) was screened in transfected HEK293 cells by using Ca(2+)-influx measurements. RESULTS: Klotho and beta-glucuronidase have been found to significantly increase the activity of TRPV5 and TRPV6, but had no effect on TRPV4 and TRPM6. Furthermore, deglycosylation by endoglycosidase-F also stimulated the activity of TRPV4, TRPV5 and TRPV6, but not of TRPM6. CONCLUSIONS: These results suggest a modulating effect for klotho primarily restricted to the epithelial Ca(2+) channels TRPV5 and TRPV6.|Calcium Channels/drug effects/*metabolism[MESH]|Calcium/metabolism[MESH]|Cell Line[MESH]|Epithelial Cells/*drug effects/*metabolism[MESH]|Glucuronidase/*pharmacology[MESH]|Humans[MESH]|Kidney Tubules, Distal/*drug effects/*metabolism[MESH]|Klotho Proteins[MESH]|Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase/pharmacology[MESH]|TRPV Cation Channels/drug effects/*metabolism[MESH]|Transfection[MESH] |
