10779/rcsi.10786514.v1
Mustapha Irnaten
Mustapha
Irnaten
Nicolas Blanchard-Gutton
Nicolas
Blanchard-Gutton
Jeppe Praetorius
Jeppe
Praetorius
Brian J. Harvey
Brian J.
Harvey
Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells.
Royal College of Surgeons in Ireland
2019
Animals
Calcium
Calcium Channels
Cell Line
Electrophysiological Processes
Estradiol
Gene Expression Regulation
Gene Knockdown Techniques
Intracellular Space
Kidney
Male
Patch-Clamp Techniques
RNA
Small Interfering
Rats
Ruthenium Red
TRPV Cation Channels
Time Factors
Molecular Medicine
2019-11-22 16:39:13
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Rapid_effects_of_17beta-estradiol_on_TRPV5_epithelial_Ca2_channels_in_rat_renal_cells_/10786514
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.