title: Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.
abstract: 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.
authors.affiliation: Department of Integrative Medical Biology, Section for Physiology, Umeå University, Umeå, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Druzin
authors.forename: Evgenya
authors.initials: E
authors.lastname: Malinina
authors.forename: Ola
authors.initials: O
authors.lastname: Grimsholm
authors.forename: Staffan
authors.initials: S
authors.lastname: Johansson
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015221:Potassium Channels / Q000494:pharmacology*; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015221:Potassium Channels; D004958:Estradiol