Diminished paracrine regulation of the epithelial Na+ channel by purinergic signaling in mice lacking connexin 30

Elena Mironova, Janos Peti-Peterdi, Vladislav Bugaj, James D. Stockand

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


We tested whether 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 wildtype 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-/- versus wild-type mice, particularly with high sodium intake. This 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 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. This loss of the ability of ENaC to respond to changes in sodium levels contributes to salt-sensitive hypertension in Cx30-/- mice.

Original languageEnglish (US)
Pages (from-to)1054-1060
Number of pages7
JournalJournal of Biological Chemistry
Issue number2
StatePublished - Jan 14 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Diminished paracrine regulation of the epithelial Na+ channel by purinergic signaling in mice lacking connexin 30'. Together they form a unique fingerprint.

Cite this