A receptor-independent effect of estrone sulfate on the hERG channel

We recently reported that physiological concentrations of 17β-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 17β-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.