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A novel Na + transport system in the A‐type intercalated cells of the CCD that mediates Na + secretion through a H/K‐ATPase type 2‐dependent pathway
Author(s) -
Edwards Aurelie,
Morla Luciana,
Walter Christine,
Doucet Alain,
Crambert Gilles
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.856.15
Subject(s) - amiloride , paracellular transport , reabsorption , chemistry , transcellular , bumetanide , biophysics , epithelial sodium channel , ion transporter , ouabain , renal sodium reabsorption , renal physiology , sodium–hydrogen antiporter , sodium , biochemistry , membrane , biology , organic chemistry , permeability (electromagnetism) , renal function
In the last few years, our understanding of the manner in which the cortical collecting duct (CCD) transports Na + has significantly evolved. Indeed, in addition to the classical ENaC‐mediated Na + reabsorption by principal cells, it has been shown that an electroneutral coupled transport system expressed in B‐type intercalated cells involving pendrin and a Na + /Cl − /HCO 3 − exchanger (NDBCE) also contributes to renal Na + reabsorption (1). In the present study, we used in vitro microperfusion experiments in the presence of the transepithelial ion concentration gradients that prevail in vivo (asymmetric conditions), combined with the predictions of a mathematical model, to fully characterize the relevant Na + transport systems in the CCD of Na + ‐depleted mice. Under these asymmetric conditions, we first assessed the contribution of the paracellular route to Na + transport by inhibiting all known and possible transcellular pathways with amiloride, hydrochlorothiazide (HCTZ), Schering 28080, and bumetanide. Under these conditions, the CCD excreted Na + (J Na = − 16.8 ± 0.8 pmol/min/mm; n = 5) whereas the Cl − flux was negligible (J Cl = − 3.4 ± 2.4 pmol/min/mm), and the transepithelial voltage (DV te ) was – 12.8 ± 1.8 mV. To estimate the contribution of each cell type, we then removed one or more inhibitors. Removal of amiloride abolished J Na showing that Na + reabsorption by principal cells counterbalances Na + secretion via the paracellular route. Conversely, removal of all inhibitors except amiloride increased Na + secretion (J Na = −32 ± pmol/min/mm,) in wild‐type mice but not in H/K‐ATPase type 2 (HKA2) knock‐out mice or in the presence of bumetanide. Altogether our results indicate that type A intercalated cells mediate the secretion of Na + via basolateral Na + ‐K + ‐2Cl − (NKCC1) cotransporters in tandem with HKA2 pumps functioning as apical Na + pumps. We have therefore identified a third CCD transcellular sodium transport pathway, in A‐type intercalated cells, which mediates Na + secretion in the CCD. Support or Funding Information Supported by a Nestlé Waters Grant