INDUCED ALTERATIONS IN CALCIUM-UPTAKE RATE IN NORMOXIC RAT PROXIMAL TUBULES

This study in well-oxygenated freshly isolated rat proximal tubules (R PT), examined the effects of several drugs that alter the transmembran e K+ and Na+ gradients across cell membranes, including valinomycin (V AL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high e xtracellular potassium chloride (KCI) concentration (45 mM) and low ex tracellular sodium concentration (100 mM) were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p <.02), from 2.9 to 3.7 with AMPHO (p <.05), from 3 .6 to 4.1 with OUAB (p <.05), and from 3.2 to 4.8 with 45 mM KCl (p <. 001). Ca2+ uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged le ss than 15% in control tubules and did not increase significantly exce pt in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p <.001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p <.001). Treatment with verapamil reduced Ca2+ uptak e rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p <.02, in AMPH O-treated RPT (from 3.8 to 3.1 p <.001), in OUAB-trented tubules (from 4.0 to 3.4, p <.01), and in KCI-treated RPT (from 3.7 to 3.2, p <.01) . These results indicate that acute changes in the transmembrane ion g radient in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ up take rates are also increased during O-2 deprivation in RPT a situatio n in which the transmembrane ion gradient is likewise altered. The inc reased Cn(2+) uptake rate observed in the present study and during hyp oxia may have a common basis, that is, altered transmembrane ion gradi ents or some function thereof.