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

HypothesisPotassium (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.ExperimentalHuman large-conductance Ca2+-activated K+ channels (BKCa) and human voltage-gated K+ channels (KV1.5) were expressed in Xenopus oocytes, and K+ currents elicited by voltage clamp were measured.ResultsBoth 17β-estradiol and BSA-conjugated 17β-estradiol increased the BKCa current in a concentration-dependent manner and this effect was abolished by tetraethylammonium ions and iberiotoxin (putative BKCa channel blockers). 17β-estradiol-stimulated increase in the BKCa 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 BKCa current in the absence or presence of NS 1619 (BKCa channel activator). Progesterone also inhibited 17β-estradiol-stimulated increase in the BKCa current. Finally, progesterone but not 17β-estradiol reduced the KV1.5 current.ConclusionsThe present results show that 17β-estradiol stimulates BKCa channels without affecting KV1.5 channels. This effect is ICI 182,780-insensitive and is likely mediated via a membrane-bound binding site. Progesterone inhibits both BKCa- and KV1.5-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 BKCa channels.