Peptide inhibition of ENaC

Iskander I. Ismailov, Vadim Gh Shlyonsky, Engin H. Serpersu, Catherine M. Fuller, Herbert C. Cheung, Donald Muccio, Bakhrom K. Berdiev, Dale J. Benos

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Liddle's disease is an autosomal dominant form of human hypertension resulting from a basal activation of amiloride-sensitive Na+ channels (ENaC). This channel activation is produced by mutations in the β- and/or γ-carboxy-terminal cytoplasmic tails, in many cases causing a truncation of the last 45-76 amino acids. In this study, we tested two hypotheses; first, β- and γ-ENaC C-terminal truncation mutants (β(ΔC) and γ(ΔC)), in combination with the wild-type α-ENaC subunit, reproduce the Liddle's phenotype at the single channel level, i.e., an increase in open probability (P(o)), and second, these C-terminal regions of β- and γ-ENaC act as intrinsic blockers of this channel. Our results indicate that αβ(ΔC)γ(ΔC)-rENaC, incorporated into planar lipid bilayers, has a significantly higher single channel P(o) compared to the wild-type channel (0.85 vs 0.60, respectively), and that 30-mer synthetic peptides corresponding to the C-terminal region of either β- or γ-ENaC block the basal-activated channel in a concentration-dependent fashion. Moreover, there was a synergy between the peptides for channel inhibition when added together. We conclude that the increase in macroscopic Na+ reabsorption that occurs in Liddle's disease is at least in part due to an increase in single channel P(o) and that the cytoplasmic tails of the β- and γ-ENaC subunits are important in the modulation of ENaC activity.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalBiochemistry
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 5 1999
Externally publishedYes

Fingerprint

Peptides
Tail
Chemical activation
Lipid bilayers
Amiloride
Lipid Bilayers
Modulation
Hypertension
Phenotype
Amino Acids
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ismailov, I. I., Shlyonsky, V. G., Serpersu, E. H., Fuller, C. M., Cheung, H. C., Muccio, D., ... Benos, D. J. (1999). Peptide inhibition of ENaC. Biochemistry, 38(1), 354-363. https://doi.org/10.1021/bi981979s

Peptide inhibition of ENaC. / Ismailov, Iskander I.; Shlyonsky, Vadim Gh; Serpersu, Engin H.; Fuller, Catherine M.; Cheung, Herbert C.; Muccio, Donald; Berdiev, Bakhrom K.; Benos, Dale J.

In: Biochemistry, Vol. 38, No. 1, 05.01.1999, p. 354-363.

Research output: Contribution to journalArticle

Ismailov, II, Shlyonsky, VG, Serpersu, EH, Fuller, CM, Cheung, HC, Muccio, D, Berdiev, BK & Benos, DJ 1999, 'Peptide inhibition of ENaC', Biochemistry, vol. 38, no. 1, pp. 354-363. https://doi.org/10.1021/bi981979s
Ismailov II, Shlyonsky VG, Serpersu EH, Fuller CM, Cheung HC, Muccio D et al. Peptide inhibition of ENaC. Biochemistry. 1999 Jan 5;38(1):354-363. https://doi.org/10.1021/bi981979s
Ismailov, Iskander I. ; Shlyonsky, Vadim Gh ; Serpersu, Engin H. ; Fuller, Catherine M. ; Cheung, Herbert C. ; Muccio, Donald ; Berdiev, Bakhrom K. ; Benos, Dale J. / Peptide inhibition of ENaC. In: Biochemistry. 1999 ; Vol. 38, No. 1. pp. 354-363.
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