The basolateral cell membrane of the rat proximal tubule contains a Na+-Ca2+ exchanger that may participate in the regulation of cytosolic calcium (Ca(i)) and Ca2+ transport. In this work, the activity and orientation of the Na+-Ca2+ exchanger was studied in rat proximal tubules. The experiments were based on the thermodynamic notion that the exchanger is driven by the prevalence of either of two electrochemical gradients, that for Na+ (ΔμNa+) or for Ca2+ (ΔμCa2+). Reductions in ΔμNa+, achieved by lowering extracellular Na+ (Na(o)) from 150 to 15 mM, increased Ca(i), decreased 45Ca efflux, and increased 45Ca influx. These changes occurred concurrently. When ΔμNa+ was reduced by increasing intracellular Na+ (Na(i)) with 10-3 M ouabain, Ca(i) also increased. The effect of ouabain was probably dependent on Na(i) accumulation because the surge in Ca(i) was prevented by exposure of the tubules to 5 mM Na(o) before ouabain exposure. On the other hand, when ΔμNa+ was lowered sequentially, by first exposing the tubules to ouabain in 150 mM Na(o) and then by reducing Na(o) to 15 mM, Ca(i) rose in two additive stages. We conclude from these data that in the rat proximal tubule the basal state of the Na+-Ca2+ exchanger is in forward mode, Na(o)-Ca(i). Moreover, the function of the Na+-Ca2+ exchanger is in accord with predictions derived from a thermodynamic analysis of its function.
|Original language||English (US)|
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - Jan 1 1989|
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