The K–Cl cotransporter-3 in the mammalian kidney

Abstract

Purpose of review We recently localized a new K–Cl cotransporters-3 (KCC3) transporter to the apical membrane of type-B intercalated cells. This gives us an opportunity to revisit the roles of the KCC3 in kidney and integrate the new findings to our current knowledge of the biology of the bicarbonate secreting cells. Recent findings Here, we review the basic properties of the K–Cl cotransporter with a particular attention to the responsiveness of the transporter to cell swelling. We summarize what is already known about KCC3b and discuss new information gained from our localizing of KCC3a in type-B intercalated cells. We integrate the physiology of KCC3a with the main function of the type-B cell, that is, bicarbonate secretion through the well characterized apical Cl−/HCO3 − exchanger and the basolateral Na-HCO3 cotransporter. Summary Both KCC3b and KCC3a seem to be needed for maintaining cell volume during enhanced inward cotransport of Na-glucose in proximal tubule and Na-HCO3 in intercalated cells. In addition, apical KCC3a might couple to pendrin function to recycle Cl−, particularly in conditions of low salt diet and therefore low Cl− delivery to the distal tubule. This function is critical in alkalemia, and KCC3a function in the pendrin-expressing cells may contribute to the K+ loss which is observed in alkalemia.

Novel functions of the anion exchanger AE4 (SLC4A9)

“…However, the assumption that AE4 can function as a Cl - extruder and a HCO 3 - loader in these cells is very appealing (Fig. 2 E) [ 19 ]. Furthermore, a change in extracellular electrolyte concentrations during metabolic acid-base imbalances could influence the [HCO 3 - ] gradient across the basolateral membrane.…”