Calcium channels activated by endothelin-1 in human trophoblast

• Published in: The Journal of physiology 2004-12, Vol.561 (2), p.449-458
• Main Authors: Niger, C., Malassiné, A., Cronier, L.
• Format: Article
• Language: English
• Subjects: Calcium Channels - metabolism; Calcium Signaling - drug effects; Calcium Signaling - physiology; Cells, Cultured; Endothelin-1 - pharmacology; Female; Humans; Pregnancy; Research Papers; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Trophoblasts - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2004.073023

Ca 2 + transfer across the syncytiotrophoblast (ST) of the human placenta is essential for normal fetal development. However, the nature of Ca 2 + 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 Ca 2 + , we used ET1 to analyse the nature of Ca 2 + channels on cultured trophoblastic cells by means of cytofluorimetric analysis using the ratiometric Ca 2 + indicator Indo-1. Results indicate that ET1 (10 −7 m ) stimulates a biphasic (transient and sustained) increase in [Ca 2 + ] 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 μ m ) totally abolished the response. Persistence of the rapid transient rise in [Ca 2 + ] i in Ca 2 + -free extracellular medium confirms the release of Ca 2 + from intracellular stores in response to ET1 stimulation. Furthermore, abolition of the sustained increase in [Ca 2 + ] i in Ca 2 + -free extracellular medium argues in favour of the entry of Ca 2 + during the plateau phase. Abolition of this plateau phase by Ni 2 + (1 m m ) in the presence of extracellular Ca 2 + confirmed the existence of an ET1-induced Ca 2 + entry. No evidence for the presence of voltage-operated channels was demonstrated during ET1 action since nifedipine (10 −6 m ) did not reduce the Ca 2 + response and depolarization with a hyper-potassium solution had no effect. Pharmacological studies using the imidazole derivatives SK&F96365 (30 μ m ) and LOE 908 (10 μ m ) partially inhibited the ET1-evoked Ca 2 + response, thus providing evidence for the presence of both store-operated Ca 2 + channels and non-selective cationic channels in the human ST.