Premium
Renal proximal tubule function is preserved in Cftr tm2cam ΔF508 cystic fibrosis mice
Author(s) -
Kibble J. D.,
Balloch K. J. D.,
Neal A. M.,
Hill C.,
White S.,
Robson L.,
Green R.,
Taylor C. J.
Publication year - 2001
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.1469-7793.2001.0449f.x
Subject(s) - cystic fibrosis , chemistry , medicine , endocrinology , forskolin , renal function , kidney , biology , receptor
1 Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftr tm2cam ΔF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT‐PCR and whole‐cell patch clamping. 2 Renal Na + clearance was similar in wild‐type (1.4 ± 0.3 μl min −1 , number of animals, N = 12) and CF mice (1.6 ± 0.4 μl min −1 , N = 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild‐type (7.0 ± 0.8 μl min −1 , N = 8) and CF mice (9.3 ± 1.4 μl min −1 , N = 9); no difference between genotypes was observed. 3 In situ microperfusion revealed that fluid absorptive rate ( J v ) was similar under control conditions between wild‐type (2.2 ± 0.4 nl mm −1 min −1 , n = 10) and CF mice (1.9 ± 0.3 nl mm −1 min −1 , n = 11). Addition of a forskolin‐dibutyryl cAMP (db‐cAMP) cocktail to the perfusate caused no significant change in J v in either wild‐type (2.6 ± 0.7 nl mm −1 min −1 , n = 10) or Cftr tm2cam ΔF508 mice (2.0 ± 0.5 nl mm −1 min −1 , n = 10). 4 CFTR expression was confirmed in samples of outer cortex using RT‐PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin‐db‐cAMP using whole‐cell patch clamping. 5 In conclusion, no functional deficit in proximal tubule function was found in Cftr tm2cam ΔF508 mice. This may be a consequence of a lack of whole‐cell cAMP‐dependent Cl − conductance in mouse proximal tubule cells.