title: Hypoxia-induced cytosolic calcium decrease is mediated primarily by the forward mode of Na(+)/Ca(2+) exchanger in smooth muscle cells of fetal ductus arteriosus.
abstract: Closure of the ductus arteriosus (DA) after birth, essential for postnatal adaptation, is initiated by the transition from hypoxia to normoxia. The current study investigated how hypoxia affects the level of cytosolic calcium ([Ca(2+)](i)) in fetal lamb DA smooth muscle cells (DASMCs) and the role of calcium pumps in this process. The [Ca(2+)](i) variation in response to acute hypoxia was determined spectrofluorometrically with fura-3-AM in cultured fetal DASMCs. Interventions using chemicals or solutions including thapsigargin, vanadate, KB-R7943, alkaline PH9.0 solution, or Na(+)-free medium were administered when samples were exposed to acute hypoxia. The results show that [Ca(2+)](i) decreased dramatically under acute hypoxia. This decrease was not attenuated completely by an inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+) adenosine triphosphatase (ATPase) (SERCA), a blocker of plasma membrane Ca(2+) ATPase (PMCA), or an inhibitor and activator of the reserve mode of the Na(+)/Ca(2+) exchanger (NCX). In contrast, KT-R9743, an inhibitor of the forward mode of NCX at a high concentration (30 microm), greatly diminished the hypoxia-induced [Ca(2+)](i) decrease in fetal DASMCs. These results suggest that a hypoxia-induced Ca(2+) decrease in fetal DASMCs results from cytosolic Ca(2+) efflux mediated primarily by the forward mode of NCX.
authors.affiliation: Department of Cardiac and Thoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Haifa
authors.initials: H
authors.lastname: Hong
authors.forename: Huiwen
authors.initials: H
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Cai
authors.forename: Yanjuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Meng
authors.initials: M
authors.lastname: Yin
authors.forename: Jinfen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004373:Ductus Arteriosus / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012756:Sheep; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019831:Sodium-Calcium Exchanger; D014638:Vanadates; D019284:Thapsigargin; D013890:Thiourea; D002118:Calcium