CALCIUM REGULATION AND TRANSPORT BY POLYCYSTIN-2 IN TERM HUMAN Syncytiotrophoblast

N MONTALBETTI, GA TIMPANARO, MR CANTERO Y HF CANTIELLO

Los Cocos, Córdoba

Congreso; III Latin American Symposium on Maternal-Fetal Interaction and Placenta: Basic & Clinical Research; 2007

Placental transfer of maternal calcium (Ca2+) is carried out by the syncytiotrophoblast. The human syncytiotrophoblast (hST) expresses abundant polycystin-2 (PC2, TRPP2), a TRP-type Ca2+-permeable nonselective cation channel. PC2 shows a weak preferential  permeability to divalent cations, including Ca2+. Polycystin-like (PCL, TRPPL) shares  significant sequence homology and similar topology with PC2. In PCL the presence of Ca2+ induces both channel activation and inactivation. In the present study, we investigated  the properties of Ca2+ transport through PC2 in hST and the possible role of this  cation in PC2 channel regulation. The hST membranes were reconstituted in a lipid bilayer chamber, in the presence of a K+ chemical gradient to assess cation channel activity.  This activity was followed with a patch-clamp amplifier and signals were processed for single channel analysis. Acute addition of EGTA (1 mM) to the cis chamber (intracellular side), containing 10 mM Ca2+ rapidly inhibited PC2-mediated cation channel activity. Further addition of Ca2+ (90 mM) to the trans side increased the substate residence distribution, and a decrease in single channel currents, associated with flickering among the various substates. These data suggest that cytosolic Ca2+ is an activating factor in PC2 channel function, and that Ca2+ transport through PC2 elicits both channel activation and a subsequent Ca2+-induced inactivation. The fact that Ca2+ transport through PC2 modifies the residence time for the various subconductance states of the channel may provide a hint as to the presence of a novel Ca2+-induced inactivating mechanism