Fetal growth is dependent on the placental supply of nutrients derived from the maternal circulation, including sodium, potassium and chloride. In addition to being essential elements for fetal development, gradients of these ions formed across the microvillous and basal membranes of the syncytiotrophoblast perform several important roles. Transmembrane ion gradients drive the uphill transport of key nutrients such as calcium, phosphate and the amino acids into the fetal circulation. They are also involved in functions such as intracellular pH and volume regulation. The studies in this proposal are designed to elucidate the major ion transport systems in the placenta and their coupling to the supply of substrates for fetal growth. The investigations will use plasma membrane vesicles prepared from the microvillous and basal membranes of term, human placental syncytiotrophoblast. The experiments are designed to identify and characterize the ion transporters for sodium, potassium, chloride, bicarbonate and H+/OH- on both membranes. A combination of fluorescence and radiolabelled tracer methods will be employed to measure the kinetic and conductive characteristics of membrane ion transport. The pathways for the maternofetal transfer of calcium, phosphate and amino acids will be defined and the coupling of ion gradients to the transport of these essential fetal nutrients will be analyzed. The final element in the project will be investigation of the method by which the intracellular calcium concentration controls placental membrane ion permeabilities. Over the short term, these studies will provide important physiological information on the manner in which the major ions, calcium phosphate and the amino acids are channeled to the fetus. The long term goals of these studies are to determine how placental functions, including transfer processes, are affected by pathological events such as hypoxia or ischemia which cause acute or chronic disturbances in the placental ionic environment.
