American journal of physiology. Renal physiology
-
Am. J. Physiol. Renal Physiol. · Jul 2003
Ammonium transport and pH regulation by K(+)-Cl(-) cotransporters.
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. ⋯ 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.
-
Am. J. Physiol. Renal Physiol. · Jul 2003
Cloning and localization of KCC4 in rabbit kidney: expression in distal convoluted tubule.
Cl-dependent K secretion is a feature of renal distal tubules and collecting ducts. Recent cloning and identification of K-Cl cotransporter proteins led us to search for additional novel KCC isoforms expressed in the renal distal nephron. A human expressed sequence tag (EST) with high homology to KCC1 was identified. ⋯ The distal convoluted tubule and connecting tubule exhibited the highest level of KCC4 immunoreactivity, followed by the medullary thick ascending limb. A low level of immunoreactivity was detected in the proximal tubule and collecting ducts. We postulate that KCC4 mediates potassium and chloride exit from the cell and may play an important role in salt absorption by the distal convoluted tubule.