We developed a dynamic model of a rat proximal convoluted tubule cell in order to investigate cell volume regulation mechanisms in this nephron segment. We examined whether regulatory volume decrease (RVD), which follows exposure to a hyposmotic peritubular solution, can be achieved solely via stimulation of basolateral K^+ and Cl^− channels and Na^+–HCO₃^− cotransporters. We also determined whether regulatory volume increase (RVI), which follows exposure to a hyperosmotic peritubular solution under certain conditions, may be accomplished by activating basolateral Na^+/H^+ exchangers. Model predictions were in good agreement with experimental observations in mouse proximal tubule cells assuming that a 10% increase in cell volume induces a fourfold increase in the expression of basolateral K+ and Cl− channels and Na+–HCO₃^− cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, Na^+–HCO₃^− cotransporters are more efficient than basolateral K^+ and Cl^− channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular Na^+ reabsorption, that is, to limit the net Na^+ flux decrease during a hyposmotic challenge or the net Na^+ flux increase during a hyperosmotic challenge.This research was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, via grant R01DK106102 to AT Layton. (R01DK106102 - National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases)Accepted manuscrip
