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The early part of the aldosterone sensitive distal nephron is the primary site of increased sodium absorption in a mouse model for Liddle’s syndrome (892.25)
Author(s) -
Korbmacher Christoph,
Bertog Marko,
Dahlmann Anke,
Nesterov Viatcheslav
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.892.25
Subject(s) - epithelial sodium channel , aldosterone , endocrinology , medicine , renal sodium reabsorption , amiloride , nephron , reabsorption , distal convoluted tubule , chemistry , mineralocorticoid , sodium , sodium channel , tubule , kidney , organic chemistry
Liddle’s syndrome (pseudohyperaldosteronism) is caused by gain‐of‐function mutations of the epithelial sodium channel (ENaC) and clinically mimics hyperaldosteronism with severe salt‐sensitive hypertension. ENaC is expressed in the aldosterone sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). In the cortical collecting duct (CCD) ENaC is known to be regulated by aldosterone. In contrast, we recently reported aldosterone‐independent ENaC regulation in the early part of the ASDN (Nesterov V et al. Am J Physiol Renal Physiol 2012, 303:F1289‐99). Here we investigated ENaC function in the transition zone of the DCT2/CNT or the CNT/CCD in a mouse model for Liddle’s syndrome. Whole‐cell amiloride‐sensitive ENaC currents (ΔIami) were measured in microdissected nephron fragments from mice maintained on different sodium diets to vary plasma aldosterone levels. Our data indicate that the primary site of increased sodium reabsorption in mice with Liddle’s syndrome is the DCT2/CNT. Compensatory suppression of plasma aldosterone is likely to mask at least in part the stimulatory effect of Liddle’s syndrome mutation on ΔIami in CNT/CCD. Our findings highlight the importance of ENaC function and regulation in the DCT2/CNT for the maintenance of sodium balance and for blood pressure control.