Regulation by Calcium of Syncytiotrophoblast polycystin-2

CANTIELLO, HORACIO FABIO Y CANTERO, MARÍA DEL ROCÍO

Santiago de Chile, Chile

Congreso; Fetus and Placenta: A Perfect Harmony. IFPA meeting 2010; 2010

Introduction: Transient receptor potential (TRP) channels contribute to important sensory functions. Polycystin-2 (TRPP2, PC2) is a large conductance, non-selective cation channel, which permeates Ca2+. PC2 is abundantly expressed in term human syncytiotrophoblast (hST) and is postulated as a principal contributor to Ca2+ delivery from mother to foetus. TRPC1 is a store- and receptor-operated channel, which is also implicated in Ca2+ entry. Both are co-expressed in the primary cilium of renal epithelial cells. Recent studies demonstrated that PC2 and TRPC1 assemble to form functional hetero-complexes with distinct functional properties. The PC2/TRPC1 complexes show a single-channel conductance, ionic permeability and pH dependence, which are distinct from those of either PC2 or TRPC1 alone. Little is known however, about Ca2+ regulation of either TRP channel complex. In this study we review regulatory mechanisms of channel function and assessed the response to Ca2+ of either complex. Methods: In vitro translated PC2 and TRPC1, hST PC2 and purified TRPC1/PC2 hetero-complexes, were assessed for their response to Ca2+. Channels were reconstituted in a lipid bilayer system exposed to a K+ chemical gradient (150/15 mM). The Ca2+ chelating agents BAPTA and EGTA were added to the cytosolic side to a final Ca2+ concentration of 0.3 nM. Results: The hST PC2 channel activity was inhibited by 70-100% in low cytosolic Ca2+. Proteins extrinsic to the channel mediated this inhibitory effect. Similar experiments conducted with TRPC1, showed Ca2+ sensitivity with a bell shaped Boltzmann´s open probability in response to Ca2+. Reducing cytosolic Ca2+ did not change either the I-V curve or the open probability of the PC2/TRPC1 hetero-complex. Discussion: The interaction between TRPC1 and PC2 in the hetero-complex may confer different biophysical and physiological properties that the observed in the homo-tetramers. Thus, Ca2+ is transported by, and regulates the function of TRP channel activity present in the human placenta.