Ammonium carriers in medullary thick ascending limb.

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 similar to 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.