Mice heterozygous for beta-ENaC deletion have defective potassium excretion

• Published in: American journal of physiology. Renal physiology Vol. 291; no. 1; pp. F107 - F115
• Main Authors: Cao, X Renee, Shi, P Peter, Sigmund, Rita D, Husted, Russell F, Sigmund, Curt D, Williamson, Roger A, Stokes, John B, Yang, Baoli
• Format: Journal Article
• Language: English
• Published: United States 01.07.2006
• Subjects: Aldosterone - blood; Animals; Blood Pressure - drug effects; Blood Pressure - genetics; Blood Pressure - physiology; Epithelial Sodium Channels; Female; Gene Deletion; Heterozygote; Homeostasis - drug effects; Homeostasis - genetics; Homeostasis - physiology; Kidney - chemistry; Kidney - drug effects; Kidney - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Potassium - metabolism; RNA, Messenger - analysis; RNA, Messenger - genetics; Sodium - metabolism; Sodium Channels - genetics; Sodium Channels - physiology; Sodium, Dietary - pharmacology; Sodium-Potassium-Chloride Symporters - analysis; Sodium-Potassium-Chloride Symporters - physiology; Sodium-Potassium-Exchanging ATPase - analysis; Sodium-Potassium-Exchanging ATPase - drug effects; Sodium-Potassium-Exchanging ATPase - physiology
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00159.2005

The present studies were designed to determine whether mice heterozygous for deletion of beta-ENaC exhibited defects in Na+/K+ transport and blood pressure regulation. In response to an acute KCl infusion, +/-mice developed higher serum [K+] and excreted only 40% of the K+ excreted by +/+mice. After 6 days on a low (0.01%)-Na+ diet, the cumulative Na+ excretion from days 3-6 was greater for +/-mice. This low-Na+ diet caused higher serum [K+] and lower K+ excretion rates in +/-mice than in +/+mice, but the rectal potential differences were not different. Analyses of mRNA from mice on this diet showed the expected approximately 50% reduction of beta-ENaC in kidney and colon of +/-mice. Unexpectedly, the level of gamma-ENaC mRNA was similarly reduced. NHE3 mRNA was approximately 30% higher in +/-mice whereas mRNA of the Na-K-2Cl cotransporter was not different. Also unexpectedly, the amount of beta-ENaC proteins was similar in both groups of mice but there was a reduction of one form of gamma-ENaC in +/-mice. These experiments demonstrate that mice heterozygous for beta-ENaC have a small but detectable defect in their ability to conserve Na+ and a more readily apparent defect in the ability to secrete K+.