title: Pregnancy upregulates large-conductance Ca(2+)-activated K(+) channel activity and attenuates myogenic tone in uterine arteries.
abstract: Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca(2+)-activated K(+) (BK(Ca)) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K(+) current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K(+) currents to the same extent in uterine arterial myocytes. The BK(Ca) channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK(Ca) channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17β-estradiol and progesterone caused a significant increase in the BK(Ca) channel current density. Western blot analyses demonstrated a significant increase of the β1, but not α, subunit of BK(Ca) channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the β1, but not α, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the β1 subunit and BK(Ca) channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy.
authors: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University, School of Medicine, Loma Linda, CA 92350, USA.
authors: Xiang-Qun
authors: XQ
authors: Hu
authors: Daliao
authors: D
authors: Xiao
authors: Ronghui
authors: R
authors: Zhu
authors: Xiaohui
authors: X
authors: Huang
authors: Shumei
authors: S
authors: Yang
authors: Sean
authors: S
authors: Wilson
authors: Lubo
authors: L
authors: Zhang
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D017136:Ion Transport; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000096:biosynthesis* / Q000235:genetics; D024510:Muscle Development / Q000502:physiology*; D009129:Muscle Tonus; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy / Q000502:physiology*; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D012756:Sheep; D015854:Up-Regulation; D055988:Uterine Artery / Q000502:physiology*
chemical_list: D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D015240:Phorbol 12,13-Dibutyrate; D011374:Progesterone; D004958:Estradiol; D011493:Protein Kinase C; D011188:Potassium