Differential effects of estrogen and progesterone on potassium channels expressed in Xenopus oocytes

Hypothesis: Potassium (K⁺) channel activation contributes in part to estrogen-mediated vasorelaxation. However, the underlying mechanism is still unclear. We hypothesize that estrogen increases K⁺ currents via membrane-associated, non-genomic interaction and that steroid hormones have differential effects on different types of K⁺ channels. Experimental: Human large-conductance Ca²⁺-activated K⁺ channels (BK_Ca) and human voltage-gated K⁺ channels (K_V1.5) were expressed in Xenopus oocytes, and K⁺ currents elicited by voltage clamp were measured. Results: Both 17β-estradiol and BSA-conjugated 17β-estradiol increased the BK_Ca current in a concentration-dependent manner and this effect was abolished by tetraethylammonium ions and iberiotoxin (putative BK_Ca channel blockers). 17β-estradiol-stimulated increase in the BK_Ca current was unaffected by treatment with ICI 182,780 (classic estrogen receptor antagonist), tamoxifen (estrogen receptor agonist/antagonist), actinomycin D (RNA synthesis inhibitor), or cycloheximide (protein synthesis inhibitor). In contrast, progesterone reduced the BK_Ca current in the absence or presence of NS 1619 (BK_Ca channel activator). Progesterone also inhibited 17β-estradiol-stimulated increase in the BK_Ca current. Finally, progesterone but not 17β-estradiol reduced the K_V1.5 current. Conclusions: The present results show that 17β-estradiol stimulates BK_Ca channels without affecting K_V1.5 channels. This effect is ICI 182,780-insensitive and is likely mediated via a membrane-bound binding site. Progesterone inhibits both BK_Ca- and K_V1.5-encoded currents. The present results suggest that inhibition of K⁺ channels may contribute in part to its reported antagonism against 17β-estradiol-mediated vascular relaxation via BK_Ca channels. © 2007 Elsevier Inc. All rights reserved.