Mice heterozygous for beta-ENaC deletion have defective potassium excretion.
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+.
Cao
X Renee
XR
Department of Obstetrics and Gynecology, Carver College of Medicine, 463 MRF, University of Iowa, and Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
Shi
P Peter
PP
Sigmund
Rita D
RD
Husted
Russell F
RF
Sigmund
Curt D
CD
Williamson
Roger A
RA
Stokes
John B
JB
Yang
Baoli
B
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D053503:Epithelial Sodium Channels; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011188:Potassium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology; D012982:Sodium, Dietary / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000032:analysis / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000187:drug effects / Q000502:physiology
D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D012982:Sodium, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D000450:Aldosterone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium