Cell volume regulation in the proximal tubule of rat kidney proximal tubule cell volume regulation
Layton, Anita T.
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Citation (published version)Aurelie Edwards, Anita T Layton. 2017. "Cell Volume Regulation in the Proximal Tubule of Rat Kidney Proximal Tubule Cell Volume Regulation." BULLETIN OF MATHEMATICAL BIOLOGY, Volume 79, Issue 11, pp. 2512 - 2533. https://doi.org/10.1007/s11538-017-0338-6
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.
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