| 18068743 |
Wong CM, Tsang SY, Yao X, Chan FL, Huang Y: Differential effects of estrogen and progesterone on potassium channels expressed in Xenopus oocytes. Steroids. 2008 Mar;73(3):272-9. Epub 2007 Nov 4.
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 Ca (2+)-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 17beta-estradiol and BSA-conjugated 17beta-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). 17beta-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 17beta-estradiol-stimulated increase in the BK (Ca) current. Finally, progesterone but not 17beta-estradiol reduced the K (V1.5) current. CONCLUSIONS: The present results show that 17beta-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 17beta-estradiol-mediated vascular relaxation via BK (Ca) channels. |
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