Different Effects of Estrogen and Progesterone on K + Currents Expressed in Xenopus Oocytes

Abstract

Potassium channel plays an active role in the regulation of membrane potential in vascular smooth muscle and vascular tone. These channels not only participate in the physiological responses to endogenously occurring substances, but also become the therapeutic targets for many synthetic drugs. Information regarding the role of K+ channels in vascular effects of female sex steroid hormones is scarce. We previously showed that K+ channel activation contributed in part to the estrogen-mediated vasorelaxation. In order to examine further whether steroid hormones may have direct interaction with K+ channels, we have recently expressed two types of K+ channels, KCa and KV channels in Xenopus oocytes. It was found that 17ß-estradiol increased the large-conductance KCa currents in a concentration-related manner. Tetraethylammonium ions or iberiotoxin inhibited the effect of 17ß-estradiol. KCa current was increased by NS 1619 and inhibited by progesterone. BSA-conjugated estrogen also increased KCa currents. Progesterone reduced the estrogen-stimulated KCa currents. KV1.5 channels were also expressed in Xenopus oocytes and inhibited by 4-aminopyridine. Progesterone reduced the KV1.5 current, while estrogen had little effect. These results showed that estrogen could stimulate KCa channels without an effect on KV1.5 channels. Progesterone inhibited the activity of both KCa and KV1.5 channels expressed in Xenopus oocytes. Progesterone was described to antagonize the vascular action of estrogen. Inhibition of K+ channels may be involved in the reported antagonistic effect of progesterone against the estrogen-induced vasorelaxation. (supported by UPGC Direct Grant)