Peptide block of constitutively activated Na+ channels in Liddle's disease

Iskander I. Ismailov, Bakhram K. Berdiev, Catherine M. Fuller, Anne Lynn Bradford, Richard P. Lifton, David G. Warnock, James K. Bubien, Dale J. Benos

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


Hypertension is a multifactorial disorder that results in an increased risk of cardiovascular and end-stage renal disease. Liddle's disease represents a specific hypertensive disease and expresses itself in the human population as an autosomal dominant trait. Recent experimental evidence indicates that patients with Liddle's disease have constitutively active amiloride-sensitive Na+ channels and that these channels are phenotypically expressed in lymphocytes obtained from normal and affected members of the original Liddle's kindred. Linkage analysis indicates that this disease results from a deletion of the carboxy-terminal region of the β-subunit of a recently cloned epithelial Na+ channel (ENaC). We report the successful immunopurification and reconstitution of both normal and constitutively active lymphocyte Na+ channels into planar lipid bilayers. These channels display all of the characteristics typical of renal Na+ channels, including sensitivity to protein kinase A phosphorylation. We demonstrate that gating of normal Na+ channels is removed by cytoplasmic trypsin digestion and that the constitutively active Liddle's Na+ channels are blocked by a β- or γ- ENaC carboxy-terminal peptide in a GTP-dependent fashion.

Original languageEnglish
Pages (from-to)C214-C223
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1 39-1
Publication statusPublished - Jan 1996


  • amiloride
  • hypertension
  • immunopurification
  • planar lipid bilayers
  • protein purification

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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