A receptor-independent effect of estrone sulfate on the HERG channel.
We recently reported that physiological concentrations of 17beta-estradiol partially down-regulate cardiac rapidly-activating delayed rectifier K(+) currents (hERG currents) independently of estrogen-receptor signaling. To determine if other estrogens have the same effect as that of 17beta-estradiol, we investigated receptor-independent effects of estrone, estrone 3-sulfate, and estriol on hERG currents in patch-clamped estrogen-negative HEK293 cells. Only estrone 3-sulfate partially suppressed hERG currents in a receptor-independent manner by modifying the gating. The concentration-dependence of estrone 3-sulfate revealed that physiological levels of circulating estrone 3-sulfate can modulate hERG currents to the maximal extent in both women and men at any age.
Kakusaka
Shoko
S
Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Asayama
Mahoko
M
Kaihara
Asami
A
Sasano
Tetsuo
T
Suzuki
Takeshi
T
Kurokawa
Junko
J
Furukawa
Tetsushi
T
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D018408:Patch-Clamp Techniques; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*
D000072237:ERG1 Potassium Channel; D004965:Estrogen Antagonists; D004967:Estrogens; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011960:Receptors, Estrogen; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate