Trafficking of Na-K-ATPase and dopamine receptor molecules induced by changes in intracellular sodium concentration of renal epithelial cells.
Most of the transepithelial transport of sodium in proximal tubules occurs through the coordinated action of the apical sodium/proton exchanger and the basolateral Na-K-ATPase. Hormones that regulate proximal tubule sodium excretion regulate the activities of these proteins. We have previously demonstrated that the level of intracellular sodium concentration modulates the regulation of Na-K-ATPase activity by angiotensin II and dopamine. An increase of a few millimolars in intracellular sodium concentration leads to increased Na-K-ATPase activity without a statistically significant increase in the number of plasma membrane Na-K-ATPase molecules, as determined by cell surface protein biotinylation. Using total internal reflection fluorescence, we detected an increased number of Na-K-ATPase molecules in cytosolic compartments adjacent to the plasma membrane, suggesting that the increased intracellular sodium concentration induces a movement of Na-K-ATPase molecules toward the plasma membrane. While intracellular compartments containing Na-K-ATPase molecules are very close to the plasma membrane, compartments containing type 1 dopamine receptors (D1Rs) are distributed in different parts of the cell cytosol. Fluorescence determinations indicate that an increased intracellular sodium concentration induces the increased colocalization of dopamine receptors with Na-K-ATPase molecules in the region of the plasma membrane. We propose that under in vivo conditions, in response to a sodium load in the lumen of proximal tubules, an increased level of intracellular sodium in epithelial cells is an early event that triggers the cellular response that leads to dopamine inhibition of proximal tubule sodium reabsorption.
Cinelli
Angel R
AR
Department of Anatomy and Cell Biology, State University of New York at Brooklyn, Brooklyn, NY, USA.
Efendiev
Riad
R
Pedemonte
Carlos H
CH
D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004705:Endocytosis / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008856:Microscopy, Fluorescence; D009893:Opossums; D010766:Phosphorylation; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D017447:Receptors, Dopamine D1; D049452:Green Fluorescent Proteins; D012964:Sodium; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium