Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.
2011 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 5, e20213- p.Article in journal (Refereed) Published
The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K(+) channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K(+) channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-Estradiol rapidly (within seconds) and reversibly reduced the K(+) currents, showing an EC(50) value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca(2+), and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K(+) currents, membrane-impermeant forms of estradiol did not reduce the K(+) currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the K(V)-2-channel blocker r-stromatoxin-1. The time course of K(+) current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K(+), suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K(+) channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K(+) currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels.
Place, publisher, year, edition, pages
San Francisco: Public Library of Science , 2011. Vol. 6, no 5, e20213- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-53900DOI: 10.1371/journal.pone.0020213PubMedID: 21625454OAI: oai:DiVA.org:umu-53900DiVA: diva2:514009