R Todd Alexander

On average 180L of water and 1.7 Kg of salt (NaCl) are filtered by the kidneys daily. In order to maintain intravascular volume and sustain life the vast majority of this must be reabsorbed along the course of the nephron. The majority of filtered salt and water is reabsorbed from the proximal tubule. We are interested in the molecular mechanisms governing this fundamental process. The apical entry step, mediated by the electroneutral exchange of intracellular sodium for filtered protons (via NHE3), regulates this. The control of its activity is therefore a focus of our work. Not surprisingly the movement of sodium across the proximal tubule (a process intimately dependent on NHE3) contributes to the re-absorption of other ions and solutes from the pro-urne, not the least of which is calcium. Failure to absorb calcium from this nephron segment results in the wasting of this fundamental ion in the urine or hypercalciuria. This is a significant risk factor for the development of osteoporosis and kidney stones, two diseases affecting women's and children's health. The molecular details controlling calcium absorption form the proximal tubule is thus the other focus of our work.