TASK channel expression in human placenta and cytotrophoblast cells.
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+ alpha-subunit mRNAs, including TASK1, remained unaltered but the regulatory BKCa beta-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 nucleation, 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 P < .001, respectively).


CONCLUSIONS
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.
Bai
Xilian
X
Maternal and Fetal Health Research Centre, Division of Human Development, The Medical School, University of Manchester, St Mary's Hospital, Manchester, United Kingdom.
Lacey
Helen A
HA
Greenwood
Susan L
SL
Baker
Philip N
PN
Turner
Mark A
MA
Sibley
Colin P
CP
Fyfe
Gregor K
GK
D001095:Arachidonic Acids / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry; D063388:Endocannabinoids; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000502:physiology*; D016133:Polymerase Chain Reaction; D053284:Polyunsaturated Alkamides; D024683:Potassium Channels, Tandem Pore Domain / Q000032:analysis / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; C410295:KCNK5 protein, human; D009419:Nerve Tissue Proteins; D053284:Polyunsaturated Alkamides; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; C078814:anandamide