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Abstract: PO1412

Pendrin Null Mice Develop Hypokalemia During Dietary Na+ Restriction Through an Epithelial Sodium Channel-Dependent Mechanism

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Pham, Truyen D, Emory University, Atlanta, Georgia, United States
  • Verlander, Jill W., University of Florida, Gainesville, Florida, United States
  • Chen, Chao, University of Florida, Gainesville, Florida, United States
  • King, Spencer A., Emory University, Atlanta, Georgia, United States
  • Elengickal, Anthony Joseph, Emory University, Atlanta, Georgia, United States
  • Welling, Paul A., Johns Hopkins University, Baltimore, Maryland, United States
  • Wall, Susan M., Emory University, Atlanta, Georgia, United States
Background

Pendrin is an electroneutral Cl-/HCO3- exchanger expressed in the apical regions of intercalated cells. It is thought to modulate NaCl absorption, while mitigating urinary K+ loss. However, the effect of pendrin gene ablation on K+ homeostasis has not been examined directly. The purpose of this study was to determine if pendrin gene ablation reduces serum K+ concentration, the conditions under which this occurs and the mechanism(s) responsible.

Methods

Pendrin null and wild type mice were given a diet deficient in Na+, K+ and Cl- or diet supplemented with Na+, K+, Cl- and/or water. We measured urine and serum electrolytes as well as K+ channel and Cl- transporter abundance by immunoblot and immunohistochemistry.

Results

Serum K+ was ~1 mEq lower in pendrin null than in wild type mice after 7 days of the Na+, K+, Cl--deficient diet. This difference was attenuated, but not eliminated, with moderate dietary K+ supplementation. Differences were eliminated with either dietary Na+ supplementation or with ENaC blockade, while differences were enhanced when ENaC was constitutively upregulated. Further studies determined whether the lower serum K+ observed in the pendrin null mice occurs from greater urinary K+ excretion. Over the first 3 days of the Na+, K+, Cl--deficient diet, pendrin null mice develop a lower serum K+ and a higher arterial pH and HCO3- concentration, likely from greater intravascular volume contraction from their enhanced urinary Na+ excretion, although urinary K+ excretion was similar in both groups over this time period. However, starting at day 4 of the diet, the pendrin null mice excrete more K+ than the wild type mice. At day 8 of the ion-deficient diet, pendrin null mice have marked hypokalemia, likely due to both the metabolic alkalosis as well as greater urinary K+ excretion, in part, from inappropriately high Maxi-K+ channel abundance.

Conclusion

Pendrin null mice develop marked hypokalemia during dietary Na+ restriction in part due to a contraction alkalosis as well as increased urinary K+ excretion that occurs in part from relatively high Maxi K channel abundance.

Funding

  • NIDDK Support