Adam Sun

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

SummaryExperiments were performed usingin 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 onemm ouabain to, the basolateral solution [ouabain(zero-K+)] provided an index to apical cotransporter activity and was used to evaluated 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 in 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 exposure22Na+ 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 cellular22Na+ 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.

Rapid Cell Volume Regulation by the Mouse Medullary Thick Ascending Limb of Henle

In this paper, we summarize our current knowledge regarding cell volume regulation in mouse medullary thick ascending loop of Henle (MTAL) cells. It has become apparent that arginine vasopressin (ADH) plays a central role in this process (at least in certain species). During antidiuresis ADH increases the rate of NaCl absorption by the MTAL, thereby enhancing the single effect of countercurrent multiplication. In addition, ADH is required for MTAL cells to regulate their volume in the more hypertonic environment. ADH appears to activate normally quiescent basolateral Na+:H+ exchangers which mediate Na+ uptake into MTAL cells during volume regulatory increase (VRI). This action of ADH may be mediated via an increase in cytosolic calcium. The trade off for this effect of ADH appears to be that the MTAL cells are no longer able to regulate their cell volume completely following reductions in interstitial osmolality. This is a direct result of an inverse relationship between the rates of salt absorption and volume regulatory decrease (VRD). This may not present a problem for the MTAL in vivo for two reasons. First, when interstitial osmolality is increased, NaCl absorption is reduced (see [1–3]). Second, when interstitial osmolality decreases during the transition from an antidiuretic to a water diuretic state the circulating level of ADH falls, and consequently, the rapid VRD response would be restored.