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 journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number1 39-1
Publication statusPublished - Jan 1996
Externally publishedYes

Fingerprint

Epithelial Sodium Channels
Peptides
Lymphocytes
Amiloride
Lipid Bilayers
Cyclic AMP-Dependent Protein Kinases
Guanosine Triphosphate
Phosphorylation
Lipid bilayers
Trypsin
Chronic Kidney Failure
Digestion
Hypertension
Kidney
Population

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Ismailov, I. I., Berdiev, B. K., Fuller, C. M., Bradford, A. L., Lifton, R. P., Warnock, D. G., ... Benos, D. J. (1996). Peptide block of constitutively activated Na+ channels in Liddle's disease. American Journal of Physiology - Cell Physiology, 270(1 39-1).

Peptide block of constitutively activated Na+ channels in Liddle's disease. / Ismailov, Iskander I.; Berdiev, Bakhram K.; Fuller, Catherine M.; Bradford, Anne Lynn; Lifton, Richard P.; Warnock, David G.; Bubien, James K.; Benos, Dale J.

In: American Journal of Physiology - Cell Physiology, Vol. 270, No. 1 39-1, 01.1996.

Research output: Contribution to journalArticle

Ismailov, II, Berdiev, BK, Fuller, CM, Bradford, AL, Lifton, RP, Warnock, DG, Bubien, JK & Benos, DJ 1996, 'Peptide block of constitutively activated Na+ channels in Liddle's disease', American Journal of Physiology - Cell Physiology, vol. 270, no. 1 39-1.
Ismailov II, Berdiev BK, Fuller CM, Bradford AL, Lifton RP, Warnock DG et al. Peptide block of constitutively activated Na+ channels in Liddle's disease. American Journal of Physiology - Cell Physiology. 1996 Jan;270(1 39-1).
Ismailov, Iskander I. ; Berdiev, Bakhram K. ; Fuller, Catherine M. ; Bradford, Anne Lynn ; Lifton, Richard P. ; Warnock, David G. ; Bubien, James K. ; Benos, Dale J. / Peptide block of constitutively activated Na+ channels in Liddle's disease. In: American Journal of Physiology - Cell Physiology. 1996 ; Vol. 270, No. 1 39-1.
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