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.
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