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.