TY - JOUR T1 - Stimulation of Protein Kinase C Rapidly Reduces Intracellular Na<sup>+</sup> Concentration via Activation of the Na<sup>+</sup>Pump in OK Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 88 LP - 97 DO - 10.1124/mol.52.1.88 VL - 52 IS - 1 AU - Carlos H. Pedemonte AU - Thomas A. Pressley AU - Angel R. Cinelli AU - Mustafa F. Lokhandwala Y1 - 1997/07/01 UR - http://molpharm.aspetjournals.org/content/52/1/88.abstract N2 - Na+ reabsorption is regulated in proximal tubules by hormones that stimulate protein kinase C (PKC). To determine whether stimulation of PKC causes a reduction in intracellular Na+concentration ([Na+]i) that might link Na+ pump activation to increased Na+reabsorption, [Na+]i was measured in kidney cells loaded with the Na+-sensitive fluorescent indicator SBFI. Rapid digital imaging fluorescence microscopy determinations were performed in epithelial kidney cells transfected with the rodent Na+ pump α1 cDNA. In 42 determinations, the basal [Na+]i was 19.7 ± 2.4 mm. Stimulation of PKC reduced the [Na+]i to 5.6 ± 0.6 mm in ∼10 sec. This drastic change in [Na+]i requires a transient 74–120-fold increase in Na+ pump activity. After the new steady state [Na+]i is reached, the Na+ pump is 58% activated. The entry of Na+ into the cells is not affected by stimulation of PKC; therefore, the reduction in [Na+]i is exclusively dependent on activation of the Na+ pump. Accordingly, PKC stimulation does not affect the [Na+]i of cells expressing a mutant Na+ pump that is not stimulated by PKC. The decrease in [Na+]i observed in cells transfected with the rodent Na+ pump α1 cDNA is large and sufficiently fast that it is expected to stimulate rapidly passive Na+-influx into the cells, thereby accounting for the observed PKC-induced stimulation of Na+ reabsorption. ER -