Vasopressin alters the mechanism of apical Cl- entry from Na+:Cl- to Na+:K+:2Cl- cotransport in mouse medullary thick ascending limb.

Experiments were performed using in vitro perfused medullary thick ascending limbs of Henle (MTAL) and in suspensions of MTAL tubules isolated from mouse kidney to evaluate the effects of arginine vasopressin (AVP) on the K+ dependence of the apical, furosemide-sensitive Na+:Cl- cotransporter and on transport-related oxygen consumption (QO2). In isolated perfused MTAL segments, the rate of cell swelling induced by removing K+ from, and adding one mM ouabain to, the basolateral solution [ouabain(zero-K+)] provided an index to apical cotransporter activity and was used to evaluate the ionic requirements of the apical cotransporter in the presence and absence of AVP. In the absence of AVP cotransporter activity required Na+ and Cl-, but not K+, while the presence of AVP the apical cotransporter required all three ions. 86Rb+ uptake into MTAL tubules in suspension was significant only after exposure of tubules to AVP. Moreover, 22Na+ uptake was unaffected by extracellular K+ in the absence of AVP while after AVP exposure 22Na+ uptake was strictly K(+)-dependent. The AVP-induced coupling of K+ to the Na+:Cl- cotransporter resulted in a doubling in the rate of NaCl absorption without a parallel increase in the rate of cellular 22Na+ uptake or transport-related oxygen consumption. These results indicate that arginine vasopressin alters the mode of a loop diuretic-sensitive transporter from Na+: Cl- cotransport to Na+: K+: 2Cl- cotransport in the mouse MTAL with the latter providing a distinct metabolic advantage for sodium transport. A model for AVP action on NaCl absorption by the MTAL is presented and the physiological significance of the coupling of K+ to the apical Na+: Cl- cotransporter in the MTAL and of the enhanced metabolic efficiency are discussed.