The long-term goals of our research program are related to the regulation of renal tubular calcium transport. In particular, experiments will concentrate on the function of the distal convoluted tubule because of its central role in regulating the final urinary excretion of Ca. The technique of in vivo microperfusion of distal tubules will be applied to study Ca, Na and H2O transport at constant delivered load. The rat distal tubule provides a particularly useful model, as its long length allows study of the early and late portions separately; the anatomical, biochemical and functional heterogeneity make this feature attractive. Studies of mechanisms of distal Ca transport will involve measurement of transepithelial Ca activity gradients to evaluate the electrochemical gradient against which Ca is transported. The nature of the transported species (ionized or complexed) will be evaluated. Studies on regulation of distal Ca transport involve PTH-ADH interaction and effects of aldosterone and luminal bicarbonate. It is anticipated that the data generated will provide new information about mechanisms of distal Ca transport and its regulation by hormones. The project has practical implications for understanding the complications of renal disease and disorders of Ca metabolism. Experiments dealing with modification of Ca transport by acidosis and diuretics should provide insight into the pathophysiology of renal stone formation and its therapy.
