Contribution of the Na+-K+-2Cl− Cotransporter (NKCC1) to Transepithelial Transport of H+, NH4 +, K+, and Na+ in Rat Outer Medullary Collecting Duct

Abstract

ABSTRACT. In rat kidney, the “secretory” isoform of the Na-K-Cl cotransporter, NKCC1 (BSC-2), localizes to the basolateral membrane of the α intercalated cell, the acid secreting cell of the outer medullary collecting duct (OMCD). This laboratory has reported that NKCC1 mediates Cl− uptake across the basolateral membrane in series with Cl− secretion across the apical membrane in rat OMCD. NKCC1 transports NH4+, K+, and Na+ as well as Cl−; therefore, a role for the cotransporter in the process of HCl, NH4Cl, KCl, and NaCl secretion has been suggested. Thus, it was determined if bumetanide, an inhibitor of NKCC1, alters transepithelial cation transport in rat OMCD. OMCD tubules from deoxycorticosterone pivalate (DOCP)–treated rats were perfused in vitro. Hydration of CO2, rather than NH4+, provides the principle source of H+ for net acid secretion. In HCO3−/CO2-buffered solutions, no effect of bumetanide on net K+ flux was detected. Under some conditions, bumetanide addition resulted in a small reduction in secretion of net H+ equivalents. Transepithelial Na+ flux, JNa, was −1.5 ± 1.7 pmol/mm per min, values not different from zero. However, with the application of bumetanide to the bath, JNa was +5.2 ± 1.3 pmol/mm per min (P < 0.05), which indicates net Na+ absorption. In conclusion, inhibition of NKCC1 in rat OMCD changes transepithelial movement of Na+ and Cl−. The role of NKCC1 in the secretion of net H+ equivalents is small.

The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice

“…More precisely, we investigated the expression of the NKCC1 cotransporter, the form that is widely distributed throughout the body but especially abundant in the kidney. Like AQP-2, NKCC1 is expressed on the outer medullary collecting duct but on the α-intercalated cells [31]. As shown in Figure 11, the immunohistochemistry analysis revealed a reduced basal expression of NKCC1 in H 4 R −/− animals compared to their wild-type counterpart.…”

Mathematical model of ammonia handling in the rat renal medulla (891.3)

“…NH þ 4 transmural fluxes are also increased in CD, but their contribution to urinary flow of ammonia remains marginal. It is difficult to compare these values with the literature, since pathologic changes in plasma potassium levels are known to affect not only potassium concentration gradients, but also the reabsorption of water and sodium, renal ammonia production and the expression of ammonia transporters [19,27,[46][47][48][49][50]. Hence, our results only represent the isolated effect of potassium, and not a physiological scenario.…”

State of knowledge on ammonia handling by the kidney

“…As with NKCC2 in the TAL, NKCC1 in the ex vivo microperfused rat OMCD can transport NH 4 + by substitution with K + . However, its contribution to H + secretion appears to be limited [ 116 ]. This observation has been confirmed in Slc12a2 knockout mice which do not develop any defects in renal acid handling [ 68 , 118 ].…”

“…In addition to its primary role in bicarbonate production, the carbonic anhydrase II (CAII) also contributes to ammonia secretion in type A intercalated cells. Inhibiting carbonic anhydrase blocks ammonia secretion in isolated perfused OMCD [ 116 ]. It is likely that this is because CAII-dependent cytosolic H + production is required to enable parallel H + and NH 3 across the apical plasma membrane.…”