Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD.
In rat kidney the "secretory" isoform of the Na+-K+-2Cl- cotransporter (NKCC1) localizes to the basolateral membrane of the alpha-intercalated cell. The purpose of this study was to determine whether rat outer medullary collecting duct (OMCD) secretes Cl- and whether transepithelial Cl- transport occurs, in part, through Cl- uptake across the basolateral membrane mediated by NKCC1 in series with Cl- efflux across the apical membrane. OMCD tubules from rats treated with deoxycorticosterone pivalate were perfused in vitro in symmetrical HCO/CO2-buffered solutions. Cl- secretion was observed in this segment, accompanied by a lumen positive transepithelial potential. Bumetanide (100 microM), when added to the bath, reduced Cl- secretion by 78%, although the lumen positive transepithelial potential and fluid flux were unchanged. Bumetanide-sensitive Cl- secretion was dependent on extracellular Na+ and either K+ or NH, consistent with the ion dependency of NKCC1-mediated Cl- transport. In conclusion, OMCD tubules from deoxycorticosterone pivalate-treated rats secrete Cl- into the luminal fluid through NKCC1-mediated Cl- uptake across the basolateral membrane in series with Cl- efflux across the apical membrane. The physiological role of NKCC1-mediated Cl- uptake remains to be determined. However, the role of NKCC1 in the process of fluid secretion could not be demonstrated.
Wall
S M
SM
Division of Renal Diseases and Hypertension, University of Texas Medical School at Houston, 6431 Fannin, MSB 4.148, Houston, TX 77030, USA. Susan.M.Wall@uth.tmc.edu
Fischer
M P
MP
Mehta
P
P
Hassell
K A
KA
Park
S J
SJ
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D002712:Chlorides; D004232:Diuretics; D002034:Bumetanide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid