All of the studies referred to above were on
All of the studies referred to above were on microvillous membrane from hSTB; however, there is little information regarding conductances in the basal membrane. Illsley and Sellers, using a fluorescent technique, determined the relative permeabilities of cations and chloride in basal membrane vesicles. Their results showed that the permeability of Na+ is greater that the permeability of K+ and that chloride conductance is practically absent, since the permeability of Cl− relative to K+ is close to zero . Later, in 1998, Powell et al. published their flux studies concerning the mechanism of chloride transport across the basal membrane. These authors suggested that, in addition to classical transporters like anion exchangers, there were chloride-conductive pathways, that were sensitive to both DIDS and DPC .
Additionally there were studies of the transplacental transfer of chloride. These experiments were performed in sheep, rat and human placentae perfused in vitro. DIDS markedly reduced materno-fetal clearance of chloride across rat placenta perfused in situ and the transplacental chloride transfer was bidirectional , . In perfused human placental cotyledons the effect of DIDS and DPC on the materno-fetal clearance of Cl− was investigated. These data showed that approximately 16% of the total Cl− clearance was sensitive to both blockers . A direct experimental system using electrophysiological methods, to identify the chloride conductances present in the hSTB membranes was necessary.
Characteristics of placental chloride channels Placental Cl− direct thrombin inhibitors have been identified in both the plasma membranes and the intracellular organelles.
Possible roles of chloride channels in the placenta Membrane potential is a determinant component of the electrochemical gradient which is the driving force for materno-fetal solute transport across the syncytiotrophoblast. There is evidence that during gestation, the placental membrane potential value changes. A comparison of membrane potentials in villi from first trimester and human placenta at term were significantly different: −32 and −24mV, respectively. Some authors have suggested that the variation in membrane potential was a consequence of the changes in the relative contributions of potassium and chloride conductances present in the apical membrane , . In that case, the chloride channels involved in membrane potential generation could change with placental development. A posteriori, a DIDS-sensitive anion conductance that contributes to the resting potential of the syncytiotrophoblast microvillous membrane was reported . However, the nature of the apical anion channels responsible for the membrane potential has not been established but some candidates have been identified such as the Maxi-chloride channel. The placental hSTB similar to virtually all cells undergoes swelling or shrinking following changes in intracellular or extracellular osmotic pressure. In the response of placental hSTB to a hyposmotic shock it is plausible that, as in other cells, K+ and Cl− transport mechanisms may be responsible for the regulatory volume decrease. The exposure of cytotrophoblast cells to hyposmotic extracellular solutions activated Cl− channels consistent with anion efflux via volume-sensitive channels described in other cell types. Thus a whole cell Cl− conductance that is activated by hyposmotic challenge has been demonstrated in these cells , . Also in cytotrophoblast cells, the hyposmotically induced efflux was reduced by a third by both DIDS and tamoxifen . For the intact trophoblast epithelium, there are several reports of swelling-induced potassium and chloride effluxes from freshly isolated placental tissue, suggesting, by the architecture of placental explants, that volume-sensitive transport mechanisms are located at the apical membrane, , . Birdsey et al., reported that a Ba2+-sensitive K+ conductance and a DIDS-sensitive anion conductance contribute to the resting potential of the syncytiotrophoblast microvillous membrane, and that these conductances are also involved in volume regulation . In addition, Shennan (1999) described the properties of volume-activated taurine transport in human placental tissue explants and concluded , similar to previous studies , , , that placenta may release amino acids in parallel with K+ and Cl− in response to an increase in cell volume. Such studies have been an important step toward characterizing the participation of ion conductances in these important functions using intact placental villi. The placental apical Maxi-chloride channel is a possible candidate for the DIDS-sensitive anion conductance mentioned above in apical syncytiotrophoblast plasma membrane. In a number of cells, this type of channel is activated by cell swelling or patch excision from non-swollen-cells, and there are several indications that the cytoskeleton is involved in its regulation .