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TASK Channel Expression in Human Placenta and Cytotrophoblast Cells

Helen A. Lacey, PhD

Susan L. Greenwood, PhD

Philip N. Baker, DM

Mark A. Turner, MD, PhD

Colin P. Sibley, PhD

Maternal and Fetal Health Research Centre, Division of Human Development, The Medical School, University of Manchester, St Mary's Hospital, Manchester, United Kingdom

Gregor K. Fyfe, PhD

Maternal and Retal Health Research Centre, Division of Human Development, The Medical School, University of Manchester, St Mary's Hospital, Manchester M13 OJH, United Kingdom gregor.k.fyfe{at}manchester.ac.uk

Objective: The multinucleate syncytiotrophoblast is the transporting epithelium of the human placental villus, formed throughout pregnancy by fusion and differentiation of underlying mononucleate cytotrophoblast cells. Similar to other epithelia, K⁺ channels will impact on syncytiotrophoblast transport properties during its development and differentiation. Therefore we investigated expression and activity of the two-pore domain K⁺ channels TASK1 and 2 in relation to gestation and differentiation, using villous tissue from first and third trimester and cultured cytotrophoblast cells at mononucleate and multinucleate stages of culture.

Methods: Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, and ⁸⁶RB⁺ (K) efflux were used to investigate TASK channel expression and function.

Results: TASK2 mRNA expression was higher in first trimester than term (10 to 13 vs 38 to 40 weeks, P <.05). Other K⁺ -subunit mRNAs, including TASK1, remained unaltered but the regulatory BK_Ca ß-subunit, like TASK2, was higher in first trimester than term (P <.001). Immunofluorescence showed that TASK2 had an intracellular localization within the trophoblast of first trimester villi but was less abundant and restricted to stem villi at term. TASK2 also showed intracellular localization in mononucleate cytotrophoblast cells in culture and expression was lost with multinucleation. By contrast, TASK1 was localised, independently of cell mucleation, to cytotrophoblast cell plasma membranes. ⁸⁶Rb⁺ (K) efflux was measured from multinucleated cytotrophoblast cells. Both basal and pH 8.0-stimulated efflux was inhibited by the TASK1 antagonist anandamide (n = 5 for both conditions; P <.01 and <.001, resectively).

Conclusion: TASK1 and 2 are expressed in placental trophoblast cells and TASK1 activity may have a role in regulating syncytiotrophoblast homeostasis and/or solute transport functions.

Key Words: Placenta • cytotrophoblast • K+ channel • TASK • anandamide

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 1, 30-39 (2006)
DOI: 10.1016/j.jsgi.2005.10.005


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