title: Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.
abstract: The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the nature of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (<5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis.
authors.affiliation: Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Beaumont Hospital, PO Box 9063, Dublin 9, Ireland. irnatenm@yahoo.fr
authors.forename: Mustapha
authors.initials: M
authors.lastname: Irnaten
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard-Gutton
authors.forename: Jeppe
authors.initials: J
authors.lastname: Praetorius
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Harvey
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012430:Ruthenium Red / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C492241:TRPV5 protein, rat; D012430:Ruthenium Red; D004958:Estradiol; D002118:Calcium