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.
  • Author List

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

  • 270
  • Issue

  • 1 39-1