title: Differential effects of estrogen and progesterone on potassium channels expressed in Xenopus oocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Department of Physiology, Chinese University of Hong Kong, Hong Kong, China. cmw45@georgetown.edu
authors: Chi-Ming
authors: CM
authors: Wong
authors: Suk-Ying
authors: SY
authors: Tsang
authors: Xiaoqiang
authors: X
authors: Yao
authors: Franky Leung
authors: FL
authors: Chan
authors: Yu
authors: Y
authors: Huang
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D004967:Estrogens; D051666:Kv1.5 Potassium Channel; D051036:Large-Conductance Calcium-Activated Potassium Channels; D011372:Progestins; D011374:Progesterone; D004958:Estradiol