Cell Volume Regulation in the Proximal Tubule of Rat Kidney

Abstract

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 $\hbox {Cl}^-$ channels and $\hbox {Na}^+$–$\hbox {HCO}_3^-$ 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 $\hbox {Na}^+$/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 $\hbox {Cl}^-$ channels and $\hbox {Na}^+$–$\hbox {HCO}_3^-$ cotransporters. Our results also suggest that in response to a hyposmotic challenge and subsequent cell swelling, $\hbox {Na}^+$–$\hbox {HCO}^-_3$ cotransporters are more efficient than basolateral K$^+$ and $\hbox {Cl}^-$ channels at lowering intracellular osmolality and reducing cell volume. Moreover, both RVD and RVI are predicted to stabilize net transcellular $\hbox {Na}^+$ reabsorption, that is, to limit the net $\hbox {Na}^+$ flux decrease during a hyposmotic challenge or the net $\hbox {Na}^+$ flux increase during a hyperosmotic challenge.