Volume 4 Supplement 1

22nd European Workshop for Rheumatology Research

Open Access

Potassium calcium-dependant BK channel: a potential membrane target of estrogens in human osteoblasts

  • VB Breuil1,
  • G Romey2,
  • L Euller-Ziegler1,
  • B Rossi1 and
  • H Schmid-Antomarchi1
Arthritis Research & Therapy20024(Suppl 1):50

https://doi.org/10.1186/ar493

Received: 15 January 2002

Published: 4 February 2002

Estrogens have been recognized for many years for their positive effects on bone. However, their mechanisms of action are still only partially resolved. Although it is generally accepted that estrogens act at genomic level by binding to intracellular estrogen receptor, they trigger nongenomic effects mediated by plasma membrane receptor. One of these is to increase activity of the BK channel in many cells types (smooth muscle and vascular endothelium), but this has never been reported in bone. BK channels are composed of alpha (encoded by Slo gene) and beta subunits. The alpha subunit forms the K+/-selective pore, while beta subunits influence the pharmacology, kinetics, and voltage/calcium sensitivity of the BK channel. β1 and β4 subunits have been reported to mediate estrogen effects on the BK channel. In this study, we have shown that primary human osteoblasts, and 3 cell lines of human osteosarcoma (MG63, SaOs2, CAL72) express the Slo protein (western blot). Using RT-PCR, we observed in all these cells the expression of the 4 beta subunits (β1, β2, β3, β4). In electrophysiology analysis, we observed a calcium-induced potassium current of high conductance. As expected, β1 subunit expression induced Charybdotoxine and Iberiotoxine (classical inhibitors of the BK channel) resistance of the BK channel. We investigated whether 17β estradiol increased the probability of the BK channel opening (NP0). Our data indicate that 17β estradiol (5 nM) increase BK channel activity, shedding a new light on the nongenomic effects of estrogens and opening new ways for therapeutic development.

Authors’ Affiliations

(1)
INSERM U 364 Faculté de Médecine-Pasteur
(2)
CNRS U145

Copyright

© BioMed Central Ltd 2002

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