Calcium influx in human uterine epithelial RL95-2 cells triggers adhesiveness for trophoblast-like cells. Model studies on signalling events during embryo implantation.
RL95-2 is a human uterine epithelial cell line that exhibits adhesion competence on its apical surface for trophoblast-like JAR cells. Using confocal microscopy and an adhesion assay we have found that changes in intracellular free calcium ([Ca(2+)](i)) in RL95-2 cells are involved in binding of JAR spheroids. Impact of spheroids upon, and movement of spheroids across, monolayers of RL95-2 cells produced a transient increase in [Ca(2+)](i). Pretreatment of RL95-2 cells with the Ca(2+) channel inhibitor, diltiazem, reduced the [Ca(2+)](i) increase. Interestingly, resting of JAR spheroids on RL95-2 cells caused no detectable alterations in [Ca(2+)](i) although cell-cell bonds were formed during prolonged contact. However, separation of established bonds did produce an increase in [Ca(2+)](i) which could be reduced by the Ca(2+) channel blocker, SKF-96365, but not by diltiazem. SKF-96365 also reduced adhesion of JAR spheroids to RL95-2 cells. In all experiments, the increase in [Ca(2+)](i) was due to influx from the external medium, as it could be blocked both by removing extracellular Ca(2+) and by nickel. These results suggest that the plasma membrane of uterine RL95-2 cells contains two types of Ca(2+) channels that are involved in trophoblast adhesion, i.e. diltiazem-sensitive channels contributing to initiation of JAR cell binding and SKF-96365-sensitive channels participating in a feedback loop that controls the balance of bonds.
Tinel
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Max-Planck Institut für molekulare Physiologie, D-44227 Dortmund, Germany.
Denker
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HW
Thie
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D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008954:Models, Biological; D018874:Spheroids, Cellular; D014327:Trophoblasts / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000166:cytology* / Q000378:metabolism
D002121:Calcium Channel Blockers; D007093:Imidazoles; D004110:Diltiazem; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium