Identification of a functional Na+/Mg2+ exchanger in human trophoblast cells.
BACKGROUND
Ionized magnesium levels are elevated in fetal blood compared with maternal blood, suggesting that the placenta may possess an active transport mechanism for magnesium. In the present study, we sought to determine the existence of an active transport mechanism for magnesium in the placenta using cultured trophoblast cells.


METHODS
Using choriocarcinoma cells as a model system, we attempted to demonstrate the presence of a functional Na+/Mg2+ exchanger. Human choriocarcinoma JEG-3 cells cultured on glass coverslips were loaded with MAG-Fura 2-AM (5 micromol/L x 30 min) to spectrofluorometrically assess kinetics of intracellular magnesium ([Mg2+]i). Cells were superfused with various concentrations of Na+, Mg2+, Ca2+ and imipramine, a blocker of erythrocyte Na/Mg exchange. [Mg2+]i calibration was determined via Triton X-100 and EDTA.


RESULTS
Sequential lowering of extracellular Na+ caused progressively larger, transient increases in [Mg2+]i. These transient changes in [Mg2+]i were completely dependent on [Mg]o but was independent of extracellular calcium ([Ca]o). Although acute imipramine did not alter basal [Mg2+]i, imipramine eliminated the return-to-basal phase of the [Mg2+]i transient induced by low sodium medium. Increasing extracellular magnesium ([Mg]o) caused stepwise increases in [Mg2+]i.


CONCLUSIONS
The JEG-3 cells appear to possess a functional Na/Mg exchanger that functions to maintain low [Mg2+]i in cytotrophoblast cells. In addition, [Mg2+]i is acutely regulated by [Mg]o. Because placental trophoblasts are sites of maternal-fetal ion exchange, and [Mg]o is altered in preeclampsia, derangements in or modulation of this exchanger may contribute to complications of pregnancy such as pregnancy-induced hypertension, pre-eclampsia, and preterm labor.
Standley
Paul R
PR
Department of Physiology, Midwestern University, Glendale, Arizona 85308, USA.
Standley
Cynthia A
CA
D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics; D017920:Antiporters / Q000187:drug effects / Q000378:metabolism*; D002822:Choriocarcinoma / Q000378:metabolism*; D005260:Female; D006801:Humans; D007099:Imipramine / Q000493:pharmacokinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D017920:Antiporters; C046250:sodium-magnesium antiporter; D007099:Imipramine