title: Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast.
abstract: Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3-5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10-1000μM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA-sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2-dependent but causal links between the two remain to be established.
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.|St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
authors: Paula
authors: P
authors: Díaz
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.|St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
authors: Colin P
authors: CP
authors: Sibley
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.|St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.
authors: Susan L
authors: SL
authors: Greenwood
mesh_terms: D015761:4-Aminopyridine / Q000737:chemistry; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D002824:Chorionic Villi / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009336:Necrosis; D010100:Oxygen / Q000737:chemistry*; D010539:Permeability; D010920:Placenta / Q000378:metabolism*; D011188:Potassium / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012414:Rubidium Radioisotopes / Q000737:chemistry; D019789:Tetraethylammonium / Q000737:chemistry; D013997:Time Factors; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D012414:Rubidium Radioisotopes; D019789:Tetraethylammonium; D006861:Hydrogen Peroxide; D015761:4-Aminopyridine; D007770:L-Lactate Dehydrogenase; D011188:Potassium; D010100:Oxygen