Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances.
The cellular distribution of the NH2-terminal electrogenic Na+-HCO3(-) cotransporter (NBCe1) variants NBCe1-A and NBCe1-B has been investigated in rat kidney and submandibular gland (SMG) under physiological conditions and after systemic acid-base perturbations. Moreover, the in vivo data were complemented in vitro by using an immortalized cell line derived from the S1 segment of the proximal tubule (PT) of normotensive Wistar-Kyoto rats (WKPT-0293 Cl.2). NBCe1-A was basolaterally localized in PT cells, whereas NBCe1-B exhibited intracellular and basolateral distribution. SMG showed transcript and protein expression for NBCe1-A and NBCe1-B. NBCe1-B was basolaterally localized in duct cells; NBCe1-A was found intracellularly in salivary striated ducts and apically in main duct cells. Acute metabolic acidosis significantly increased cells that showed basolateral NBCe1-A in the PT, indicating increased HCO3(-) reabsorption, and significantly decreased cells that exhibited basolateral NBCe1-B in the salivary ducts, suggesting decreased HCO3(-) secretion. Chronic acidosis had no effect on NBCe1 distribution in PT but significantly increased the percentage of cells with basolateral NBCe1-A in salivary striated duct cells, suggesting increased HCO3(-) reabsorption. In contrast, chronic alkalosis caused adaptive redistribution of NBCe1-A and NBCe1-B in renal PT, favoring decreased HCO3(-) reabsorption. In vitro, WKPT-0293 Cl.2 cells expressed key acid-base transporters. Extracellular alkalosis downregulated NBCe1-A protein. WKPT-0293 Cl.2 cells are therefore a useful model to study renal acid-base regulation in vitro. The results propose redistribution of the transporters as a potential posttranslational regulation modus during acid-base disturbances. Moreover, the data demonstrate that renal PT and salivary duct epithelia respond to acid-base disturbances by an opposite redistribution pattern for NBCe1-A and NBCe1-B, reflecting specialized functions as the HCO3(-)-reabsorbing and HCO3(-)-secreting epithelium, respectively.
Brandes
Alena
A
Center for Anatomy, Dept. of Neuroanatomy, Univ. of Goettingen, Kreuzbergring 36, D-37075 Goettingen, Germany.
Oehlke
Oliver
O
Schümann
Anne
A
Heidrich
Stefanie
S
Thévenod
Frank
F
Roussa
Eleni
E
D000137:Acid-Base Imbalance / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018987:Salivary Ducts / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*; D014018:Tissue Distribution
C422004:Slc4a4 protein, rat; D027982:Sodium-Bicarbonate Symporters