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REGULATION OF ENaC BY ATP RELEASE THROUGH Cx30 IS REQUIRED FOR ALDOSTERONE ‐ ESCAPE
Author(s) -
Mironova Elena,
PetiPeterdi Janos,
Stockand James,
Bugaj Vladislav
Publication year - 2011
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.25.1_supplement.1041.7
Subject(s) - epithelial sodium channel , aldosterone , medicine , endocrinology , sodium , purinergic receptor , nephron , chemistry , excretion , atpase , kidney , biology , biochemistry , enzyme , adenosine , organic chemistry
We tested if ATP release through Connexin 30 (Cx30) is part of a local purinergic regulatory system intrinsic to the aldosterone‐sensitive distal nephron (ASDN) important for proper control of sodium excretion; if changes in sodium intake influence ATP release via Cx30, and if this allows a normal ENaC response to changes in systemic sodium levels. In addition, we define the consequences of disrupting ATP regulation of ENaC in Cx30 −/− mice. Urinary ATP levels in wild‐type mice increase with sodium intake, being lower and less dependent on sodium intake in Cx30 −/− mice. Loss of inhibitory ATP regulation causes ENaC activity to be greater in Cx30 −/− vs. wild‐type mice, particularly with high sodium intake. These results from compromised ATP release rather than end‐organ resistance: ENaC in Cx30 −/− mice responds to exogenous ATP. Thus, loss of paracrine ATP feedback regulation of ENaC in Cx30 −/− mice disrupts normal responses to changes in sodium intake. Consequently, ENaC is hyperactive in Cx30 −/− mice inappropriately lowering sodium excretion particularly during increases in sodium intake. Clamping mineralocorticoids high in Cx30 −/− mice fed a high sodium diet causes a marked decline in renal sodium excretion. This is not the case in wild‐type mice, which are capable of undergoing aldosterone‐escape. It is the loss of the ability of ENaC to respond to changes in sodium levels that causes salt‐sensitive hypertension in Cx30 −/− mice.