Kidney Week

Abstract: PO1412

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

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

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

Truyen D Pham,

• Verlander, Jill W., University of Florida, Gainesville, Florida, United States

Jill W. Verlander,

• Chen, Chao, University of Florida, Gainesville, Florida, United States

Chao Chen,

• King, Spencer A., Emory University, Atlanta, Georgia, United States

Spencer A. King,

• Elengickal, Anthony Joseph, Emory University, Atlanta, Georgia, United States

Anthony Joseph Elengickal,

• Welling, Paul A., Johns Hopkins University, Baltimore, Maryland, United States

Paul A. Welling,

• Wall, Susan M., Emory University, Atlanta, Georgia, United States

Susan M. Wall,

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