Severe hyperkalemia is rescued by low-potassium diet in renal βENaC-deficient mice.

Abstract

In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa+/LK+) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1bPax8/LC1) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1aPax8/LC1 mice without persistent salt wasting. This is followed by a marked downregulation of STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) and Na+/Cl- co-transporter (NCC) protein expression and activity. Most of the experimental Scnn1bPax8/LC1 mice survived with a HNa+/LK+ diet that partly normalized NCC phosphorylation, but not total NCC expression. Since salt loss was minor, we applied a standard-sodium/LK+ diet that efficiently rescued these mice resulting in normokalemia and normalization of NCC phosphorylation, but not total NCC expression. A further switch to LNa+/standard-K+ diet induced again a severe PHA-1-like phenotype, but with only transient salt wasting indicating that low-K+ intake is critical to decrease hyperkalemia in a NCC-dependent manner. In conclusion, while the βENaC subunit plays only a minor role in sodium balance, severe hyperkalemia results in downregulation of NCC expression and activity. Our data demonstrate the importance to primarily correct the hyperkalemia with a low-potassium diet that normalizes NCC activity.

• Authors: Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard Claude Rossier, Edith Hummler
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 469 Issue 10 Pg. 1387-1399 (10 2017) ISSN: 1432-2013 [Electronic] Germany
• PMID: 28567665 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epithelial Sodium Channels
• Potassium Channels, Inwardly Rectifying
• Sodium
• Potassium

Topics

• Animals
• Diet, Sodium-Restricted
• Epithelial Sodium Channels (metabolism)
• Hyperkalemia (metabolism)
• Kidney (metabolism)
• Mice, Transgenic
• Nephrons (metabolism)
• Phenotype
• Potassium (metabolism)
• Potassium Channels, Inwardly Rectifying (metabolism)
• Sodium (metabolism)