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1Nephrology Group, Department of Medicine, Faculty of Medicine, Université Laval, Québec G1R 2J6; and 2Groupe de Recherche en Transport Membranaire, Physics Department, Université de Montréal, Montréal, Québec, Canada H3C 3J7
Submitted 22 January 2003 ; accepted in final form 18 March 2003
The Na+-K+-Cl- cotransporters (NKCCs), which belong to the cation-Cl- cotransporter (CCC) family, are able to translocate
across cell membranes. In this study, we have used the oocyte expression system to determine whether the K+-Cl- cotransporters (KCCs) can also transport
and whether they play a role in pH regulation. Our results demonstrate that all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote
translocation, presumably through binding of the ion at the K+ site. Moreover, kinetic studies for both NKCCs and KCCs suggest that
is an excellent surrogate of Rb+ or K+ and that
transport and cellular acidification resulting from CCC activity are relevant physiologically. In this study, we have also found that CCCs are strongly and differentially affected by changes in intracellular pH (independently of intracellular [
]). Indeed, NKCC2, KCC1, KCC2, and KCC3 are inhibited at intracellular pH <7.5, whereas KCC4 is activated. These results indicate that certain CCC isoforms may be specialized to operate in acidic environments. CCC-mediated
transport could bear great physiological implication given the ubiquitous distribution of these carriers.
NKCC; KCC; ion affinity; acidification; collecting duct
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