Ammonium carriers in medullary thick ascending limb

Abstract

Absorption of NH(4)(+) by the medullary thick ascending limb (MTAL) is a key event in the renal handling of NH(4)(+), leading to accumulation of NH(4)(+)/NH(3) in the renal medulla, which favors NH(4)(+) secretion in medullary collecting ducts and excretion in urine. The Na(+)-K(+)(NH(4)(+))-2Cl(-) cotransporter (BSC1/NKCC2) ensures approximately 50-65% of MTAL active luminal NH(4)(+) uptake under basal conditions. Apical barium- and verapamil-sensitive K(+)/NH(4)(+) antiport and amiloride-sensitive NH(4)(+) conductance account for the rest of active luminal NH(4)(+) transport. The presence of a K(+)/NH(4)(+) antiport besides BSC1 allows NH(4)(+) and NaCl absorption by MTAL to be independently regulated by vasopressin. At the basolateral step, the roles of NH(3) diffusion coupled to Na(+)/H(+) exchange or Na(+)/NH(4)(+) exchange, which favors NH(4)(+) absorption, and of Na(+)/K(+)(NH(4)(+))-ATPase, NH(4)(+)-Cl(-) cotransport, and NH(4)(+) conductance, which oppose NH(4)(+) absorption, have not been quantitatively defined. The increased ability of the MTAL to absorb NH(4)(+) during chronic metabolic acidosis involves an increase in BSC1 expression, but fine regulation of MTAL NH(4)(+) transport probably requires coordinated effects on various apical and basolateral MTAL carriers.

Molecular Mechanisms of Renal Ammonia Transport

“…The furosemide-sensitive apical Na + -K + -2Cl − cotransporter NKCC2 mediates the majority of NH 4 + reabsorption; an apical K + /NH 4 + antiporter and an amiloridesensitive NH 4 + conductance also contribute (15)(16)(17). Some of the ammonia absorbed by the medullary thick ascending limb of the loop of Henle undergoes recycling into the thin descending limb of the loop of Henle; this involves passive NH 3 diffusion, with a small component of passive NH 4 + transport (18,19).…”

Evidence for ammonium conductance in a mouse thick ascending limb cell line

“…Patch clamp of ST‐1 cells also shows ${\text{NH}}_4^{+}$ conductance in the presence of barium and TEA, consistent with the report that ${\text{NH}}_4^{+}$ is poorly transported by K channels in the TAL (Attmane‐Elakeb et al. 2001). …”

“…1994; Attmane‐Elakeb et al. 2001) in the luminal membrane of the tubule, and the Na/H exchanger NHE4 (Bourgeois et al. 2010) in the basolateral membrane.…”

“…1994; Attmane‐Elakeb et al. 2001). K/NH 4 exchange is barium‐ and verapamil‐sensitive, whereas ${\text{NH}}_4^{+}$ conductance is barium‐insensitive and amiloride‐sensitive (Amlal et al.…”

Rhesus Glycoprotein P2 (Rhp2) Is a Novel Member of the Rh Family of Ammonia Transporters Highly Expressed in Shark Kidney

“…Various ion pumps or transporters such as Na ϩ /K ϩ -ATPase, Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC), K ϩ -Cl Ϫ cotransporter, and H ϩ /K ϩ -ATPase are known to accept NH 4 ϩ as substrate in place of K ϩ (for review, see Ref. 49). Among these molecules, NKCC2 is located at the apical membranes of tubular cells in the thick ascending limb of mammalian kidneys and takes up the majority of NH 4 ϩ from the luminal tract (50).…”