Ammonium carriers in medullary thick ascending limb

Abstract

Absorption of NH4 + by the medullary thick ascending limb (MTAL) is a key event in the renal handling of NH4 +, leading to accumulation of NH4 +/NH3 in the renal medulla, which favors NH4 + secretion in medullary collecting ducts and excretion in urine. The Na+-K+(NH4 +)-2Cl−cotransporter (BSC1/NKCC2) ensures ∼50–65% of MTAL active luminal NH4 + uptake under basal conditions. Apical barium- and verapamil-sensitive K+/NH4 +antiport and amiloride-sensitive NH4 + conductance account for the rest of active luminal NH4 + transport. The presence of a K+/NH4 + antiport besides BSC1 allows NH4 + and NaCl absorption by MTAL to be independently regulated by vasopressin. At the basolateral step, the roles of NH3 diffusion coupled to Na+/H+ exchange or Na+/NH4 + exchange, which favors NH4 + absorption, and of Na+/K+(NH4 +)-ATPase, NH4 +-Cl− cotransport, and NH4 + conductance, which oppose NH4 +absorption, have not been quantitatively defined. The increased ability of the MTAL to absorb NH4 + during chronic metabolic acidosis involves an increase in BSC1 expression, but fine regulation of MTAL NH4 + transport probably requires coordinated effects on various apical and basolateral MTAL carriers.