Gating of amiloride-sensitive Na+ channels

Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator

Bakhrom K. Berdiev, Vadim Gh Shlyonsky, Katherine H. Karlson, Bruce A. Stanton, Iskander I. Ismailov

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In search of the structural basis for gating of amiloride-sensitive Na+ channels, kinetic properties of single homo and heterooligomeric ENaCs formed by the subunits with individual truncated cytoplasmic domains were studied in a cell-free planar lipid bilayer reconstitution system. Our results identify the N-terminus of the α-subunit as a major determinant of kinetic behavior of both homooligomeric and heterooligomeric ENaCs, although the carboxy- terminal domains of β, and γ-ENaC subunits play important role(s) in modulation of the kinetics of heterooligomeric channels. We also found that the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits amiloride-sensitive channels, at least in part, by modulating their gating. Comparison of these data suggests that the modulatory effects of the β- and γ-ENaC subunits, and of the CFTR, may involve the same, or closely related, mechanism(s); namely, 'locking' the heterooligomeric channels in their closed state. These mechanisms, however, do not completely override the gating mechanism of the α-channel.

Original languageEnglish
Pages (from-to)1881-1894
Number of pages14
JournalBiophysical Journal
Volume78
Issue number4
Publication statusPublished - Apr 2000
Externally publishedYes

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Amiloride
Lipid Bilayers

ASJC Scopus subject areas

  • Biophysics

Cite this

Berdiev, B. K., Shlyonsky, V. G., Karlson, K. H., Stanton, B. A., & Ismailov, I. I. (2000). Gating of amiloride-sensitive Na+ channels: Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator. Biophysical Journal, 78(4), 1881-1894.

Gating of amiloride-sensitive Na+ channels : Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator. / Berdiev, Bakhrom K.; Shlyonsky, Vadim Gh; Karlson, Katherine H.; Stanton, Bruce A.; Ismailov, Iskander I.

In: Biophysical Journal, Vol. 78, No. 4, 04.2000, p. 1881-1894.

Research output: Contribution to journalArticle

Berdiev, BK, Shlyonsky, VG, Karlson, KH, Stanton, BA & Ismailov, II 2000, 'Gating of amiloride-sensitive Na+ channels: Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator', Biophysical Journal, vol. 78, no. 4, pp. 1881-1894.
Berdiev, Bakhrom K. ; Shlyonsky, Vadim Gh ; Karlson, Katherine H. ; Stanton, Bruce A. ; Ismailov, Iskander I. / Gating of amiloride-sensitive Na+ channels : Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator. In: Biophysical Journal. 2000 ; Vol. 78, No. 4. pp. 1881-1894.
@article{d80924aff36447ca96157e35ad4db861,
title = "Gating of amiloride-sensitive Na+ channels: Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator",
abstract = "In search of the structural basis for gating of amiloride-sensitive Na+ channels, kinetic properties of single homo and heterooligomeric ENaCs formed by the subunits with individual truncated cytoplasmic domains were studied in a cell-free planar lipid bilayer reconstitution system. Our results identify the N-terminus of the α-subunit as a major determinant of kinetic behavior of both homooligomeric and heterooligomeric ENaCs, although the carboxy- terminal domains of β, and γ-ENaC subunits play important role(s) in modulation of the kinetics of heterooligomeric channels. We also found that the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits amiloride-sensitive channels, at least in part, by modulating their gating. Comparison of these data suggests that the modulatory effects of the β- and γ-ENaC subunits, and of the CFTR, may involve the same, or closely related, mechanism(s); namely, 'locking' the heterooligomeric channels in their closed state. These mechanisms, however, do not completely override the gating mechanism of the α-channel.",
author = "Berdiev, {Bakhrom K.} and Shlyonsky, {Vadim Gh} and Karlson, {Katherine H.} and Stanton, {Bruce A.} and Ismailov, {Iskander I.}",
year = "2000",
month = "4",
language = "English",
volume = "78",
pages = "1881--1894",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "4",

}

TY - JOUR

T1 - Gating of amiloride-sensitive Na+ channels

T2 - Subunit-subunit interactions and inhibition by the cystic fibrosis transmembrane conductance regulator

AU - Berdiev, Bakhrom K.

AU - Shlyonsky, Vadim Gh

AU - Karlson, Katherine H.

AU - Stanton, Bruce A.

AU - Ismailov, Iskander I.

PY - 2000/4

Y1 - 2000/4

N2 - In search of the structural basis for gating of amiloride-sensitive Na+ channels, kinetic properties of single homo and heterooligomeric ENaCs formed by the subunits with individual truncated cytoplasmic domains were studied in a cell-free planar lipid bilayer reconstitution system. Our results identify the N-terminus of the α-subunit as a major determinant of kinetic behavior of both homooligomeric and heterooligomeric ENaCs, although the carboxy- terminal domains of β, and γ-ENaC subunits play important role(s) in modulation of the kinetics of heterooligomeric channels. We also found that the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits amiloride-sensitive channels, at least in part, by modulating their gating. Comparison of these data suggests that the modulatory effects of the β- and γ-ENaC subunits, and of the CFTR, may involve the same, or closely related, mechanism(s); namely, 'locking' the heterooligomeric channels in their closed state. These mechanisms, however, do not completely override the gating mechanism of the α-channel.

AB - In search of the structural basis for gating of amiloride-sensitive Na+ channels, kinetic properties of single homo and heterooligomeric ENaCs formed by the subunits with individual truncated cytoplasmic domains were studied in a cell-free planar lipid bilayer reconstitution system. Our results identify the N-terminus of the α-subunit as a major determinant of kinetic behavior of both homooligomeric and heterooligomeric ENaCs, although the carboxy- terminal domains of β, and γ-ENaC subunits play important role(s) in modulation of the kinetics of heterooligomeric channels. We also found that the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits amiloride-sensitive channels, at least in part, by modulating their gating. Comparison of these data suggests that the modulatory effects of the β- and γ-ENaC subunits, and of the CFTR, may involve the same, or closely related, mechanism(s); namely, 'locking' the heterooligomeric channels in their closed state. These mechanisms, however, do not completely override the gating mechanism of the α-channel.

UR - http://www.scopus.com/inward/record.url?scp=0034127017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034127017&partnerID=8YFLogxK

M3 - Article

VL - 78

SP - 1881

EP - 1894

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 4

ER -