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

Academic Article

Abstract

  • 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. + + + + + +
  • Digital Object Identifier (doi)

    Author List

  • Ismailov II; Berdiev BK; Fuller CM; Bradford AL; Lifton RP; Warnock DG; Bubien JK; Benos DJ
  • Volume

  • 270
  • Issue

  • 1 39-1