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Calcium channels activated by endothelin-1 in human trophoblast

By C Niger, A Malassiné and L Cronier


Ca2+ transfer across the syncytiotrophoblast (ST) of the human placenta is essential for normal fetal development. However, the nature of Ca2+ conductance in the ST and the mechanisms by which it is regulated are poorly understood. With the major signal transduction pathway of endothelin-1 (ET1) acting via phospholipase C (PLC) and Ca2+, we used ET1 to analyse the nature of Ca2+ channels on cultured trophoblastic cells by means of cytofluorimetric analysis using the ratiometric Ca2+ indicator Indo-1. Results indicate that ET1 (10−7 m) stimulates a biphasic (transient and sustained) increase in [Ca2+]i in trophoblastic cells. This response is mediated by the endothelin receptor B (ETB) coupled to PLC, since treatment with BQ788 (10−6 m) or U73122 (2 μm) totally abolished the response. Persistence of the rapid transient rise in [Ca2+]i in Ca2+-free extracellular medium confirms the release of Ca2+ from intracellular stores in response to ET1 stimulation. Furthermore, abolition of the sustained increase in [Ca2+]i in Ca2+-free extracellular medium argues in favour of the entry of Ca2+ during the plateau phase. Abolition of this plateau phase by Ni2+ (1 mm) in the presence of extracellular Ca2+ confirmed the existence of an ET1-induced Ca2+ entry. No evidence for the presence of voltage-operated channels was demonstrated during ET1 action since nifedipine (10−6 m) did not reduce the Ca2+ response and depolarization with a hyper-potassium solution had no effect. Pharmacological studies using the imidazole derivatives SK&F96365 (30 μm) and LOE 908 (10 μm) partially inhibited the ET1-evoked Ca2+ response, thus providing evidence for the presence of both store-operated Ca2+ channels and non-selective cationic channels in the human ST

Topics: Research Papers
Publisher: Blackwell Science Inc
OAI identifier: oai:pubmedcentral.nih.gov:1665371
Provided by: PubMed Central
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