Selected aspects of cell volume control in renal cortical and medullary tissue

Under normal physiological conditions, demands placed on mammalian renal cortical cells are quite different from those in the medulla. Cortical proximal tubule cells exist in an isotonic environment, but must resorb vast amounts of filtered fluid and solute, and also adjust to solute generated from cellular metabolism. In addition, cortical cells must also adjust to occasional pathological derangements in blood osmolality. By contrast, human medullary cells have a smaller solute resorptive load, but exist in a milieu where osmolality varies from 40 to more than 1200 mosmol/kg H2O, depending on water intake. Remarkably, the cells maintain a near normal size despite these stresses. Under isosmotic conditions, the primary regulator of cell volume is Na-K ATPase. In its absence, factors such as external protein, extracellular matrix and basement membrane, cytoskeleton, and perhaps formation of cytoplasmic vesicular-like structures help prevent cells from swelling massively. Under anisosmotic conditions, a variety of transport processes operating across basolateral and apical membranes either remove solute from or add solute (and water) to cells to minimize changes in their size. Medullary cells have the additional ability to accumulate organic, non-toxic, osmolytes that offset external hypertonicity and allow cells to maintain normal size without increasing cellular inorganic ion concentrations.