Premium
Evidence for cystic fibrosis transmembrane conductance regulator‐dependent sodium reabsorption in kidney, using Cftr tm2cam mice
Author(s) -
Kibble J. D.,
Neal A. M.,
Colledge W. H.,
Green R.,
Taylor C. J.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00027.x
Subject(s) - amiloride , cystic fibrosis transmembrane conductance regulator , medicine , endocrinology , reabsorption , cystic fibrosis , chemistry , natriuresis , sodium , kidney , δf508 , epithelial sodium channel , excretion , transepithelial potential difference , biology , ion transporter , biochemistry , membrane , organic chemistry
1 The aims of this study were to investigate (a) if renal Na + handling was normal in Cftr tm2cam ΔF508 cystic fibrosis mice, (b) whether adaptation to dietary salt depletion was preserved and (c) whether Cftr tm2cam ΔF508 mice exhibited enhanced amiloride‐sensitive Na + absorption. 2 In Na + ‐replete animals (maintained on a 0.32 % NaCl diet) given a 150 mM NaCl i.v. maintenance infusion, there was no difference in fractional Na + excretion (FE Na ) between wild‐type (0.42 ± 0.06 %, n = 12 ) and Cftr tm2cam ΔF508 mice (0.47 ± 0.13 %, n = 7 ). Amiloride infusion significantly increased FE Na in both wild‐type (3.14 ± 0.83 %, n = 6 ) and Cftr tm2cam ΔF508 mice (3.47 ± 0.63 %, n = 9) , though with no significant difference between genotypes. 3 A 14 day dietary salt restriction (animals maintained on a 0.03 % NaCl diet) and maintenance infusion with a 15 mM NaCl vehicle caused a reduction in FE Na to 0.14 ± 0.05 %, n = 8 in wild‐type mice and 0.14 ± 0.04 %, n = 8 in Cftr tm2cam ΔF508 mice. No significant difference in the ability to adapt to low salt conditions was apparent comparing the two genotypes. 4 Treatment of salt‐restricted mice with amiloride resulted in a blunted natriuresis in both wild‐type mice (FE Na = 1.10 ± 0.16 %, n = 7 ) and Cftr tm2cam ΔF508 mice (FE Na = 1.97 ± 0.29 %, n = 9 ). The natriuresis induced by amiloride was significantly greater in Cftr tm2cam ΔF508 mice than in wild‐type controls. 5 In conclusion, Cftr tm2cam ΔF508 mice exhibit normal renal salt excretion when either salt replete or salt restricted. Enhanced amiloride‐sensitive FE Na is consistent with increased Na + absorption via the amiloride‐sensitive sodium channel ENaC, in cystic fibrosis kidney, but this was only observed during salt restriction.