Adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity

Karl P. Roos, Vladislav Bugaj, Elena Mironova, James D. Stockand, Nirupama Ramkumar, Sara Rees, Donald E. Kohan

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Vasopressin modulates sodium reabsorption in the collecting duct through adenylyl cyclase-stimulated cyclic AMP, which exists as multiple isoforms; the specific isoform involved in vasopressin-stimulated sodium transport is unknown. To assess this, we studied mice deficient in adenylyl cyclase type VI specifically in the principal cells of the collecting duct. Knockout mice had increased urine volume and reduced urine sodium concentration, but regardless of the level of sodium intake, they did not exhibit significant alterations in urinary sodium excretion, arterial pressure, or pulse rate. Plasma renin concentration was elevated in knockout mice, however, suggesting a compensatory response. Valsartan significantly reduced arterial pressure in knockout mice but not in controls. Knockout mice had decreased renal cortical mRNA content of all three epithelial sodium channel (ENaC) isoforms, and total cell sodium channel isoforms α and γ were reduced in these animals. Patch-clamp analysis of split-open cortical collecting ducts revealed no difference in baseline activity of sodiumchannels, but knockout mice had abolished vasopressinstimulated ENaC open probability and apical membrane channel number. In summary, these data suggest that adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity in the kidney.

Original languageEnglish (US)
Pages (from-to)218-227
Number of pages10
JournalJournal of the American Society of Nephrology
Volume24
Issue number2
DOIs
StatePublished - Jan 31 2013

ASJC Scopus subject areas

  • Nephrology

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