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Publication : Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters.

First Author  Bergeron MJ Year  2003
Journal  Am J Physiol Renal Physiol Volume  285
Issue  1 Pages  F68-78
PubMed ID  12657561 Mgi Jnum  J:285019
Mgi Id  MGI:6393154 Doi  10.1152/ajprenal.00032.2003
Citation  Bergeron MJ, et al. (2003) Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters. Am J Physiol Renal Physiol 285(1):F68-78
abstractText  The Na(+)-K(+)-Cl(-) cotransporters (NKCCs), which belong to the cation-Cl(-) cotransporter (CCC) family, are able to translocate NH4(+) across cell membranes. In this study, we have used the oocyte expression system to determine whether the K(+)-Cl(-) cotransporters (KCCs) can also transport NH4(+) 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 NH4(+) translocation, presumably through binding of the ion at the K(+) site. Moreover, kinetic studies for both NKCCs and KCCs suggest that NH4(+) is an excellent surrogate of Rb(+) or K(+) and that NH4(+) 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 [NH4(+)]). 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 NH4(+) transport could bear great physiological implication given the ubiquitous distribution of these carriers.
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