Modulation of phosphate absorption by calcium in the rabbit proximal convoluted tubule

Proximal convoluted (S₂) and straight (S₃) renal tubule segments were studied to determine the effect of Ca on lumen-to-bath phosphate flux (J(PO₄)(lb)). Increasing bath and perfusate Ca from 1.8 to 3.6 mM enhanced J(PO₄) (lb) from 3.3 ± 0.7 to 6.6 ± 0.6 pmol/mm per min in S₂ segments ( < 0.001) but had no effect in S₃ segments. Decreasing bath and perfusate Ca from 1.8 to 0.2 mM reduced J(PO₄)(lb) from 3.7 ± 0.6 to 2.2 ± 0.6 in S₂ segments. These effects were unrelated to changes in fluid absorption and transepithelial potential difference. Increasing cytosolic Ca with a Ca ionophore, inhibiting the Ca-calmodulin complex with trifluoperazine, or applying the Ca channel blocker nifedipine had no effect on J(PO₄)(lb) in S₂ segments. Increasing only bath Ca from 1.8 to 3.6 mM did not significantly affect J(PO₄)(lb). However, increasing only perfusate Ca enhanced J(PO₄(lb) from 3.4 ± 0.7 to 6.1 ± 0.7 pmol/mm per min (P < 0.005). Inhibition of hydrogen ion secretion, by using a low bicarbonate, low pH perfusate, both depressed base-line J(PO₄)(lb) and abolished the stimulatory effect of raising perfusate Ca. Net phosphate efflux (J(PO₄)(net)) also increased after ambient calcium levels were raised, ruling out a significant increase in PO₄ backflux. When net sodium transport was abolished by reducing the bath temperature to 24°C, J(PO₄)(net) at normal ambient calcium was reduced and increasing ambient calcium failed to increase it, ruling out a simple physicochemical reaction wherein phosphate precipitates out of solution with calcium. The present studies provide direct evidence for a stimulatory effect of Ca on sodium-dependent PO₄ absorption in the proximal convoluted tubule, exerted at the luminal membrane. It is postulated that Ca modulates the affinity of the PO₄ transporter for the anion.