KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions

Rene Barro, Rosamary Ramentol, Sara I. Liin, Marta E. Perez, Robert S. Kass, Hans P Larsson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coas-sembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphos-phate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.

Original languageEnglish (US)
Pages (from-to)E7367-E7376
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number35
DOIs
StatePublished - Aug 29 2017

Fingerprint

Voltage-Gated Potassium Channels
Fluorometry
Mutation
Phosphatidylinositols
Action Potentials
Stomach
Potassium
Colon
Salts
Epithelial Cells
Kidney
Water

Keywords

  • KCNE1
  • KCNE3
  • KCNQ1
  • Kv7.1
  • Voltage clamp fluorometry

ASJC Scopus subject areas

  • General

Cite this

KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions. / Barro, Rene; Ramentol, Rosamary; Liin, Sara I.; Perez, Marta E.; Kass, Robert S.; Larsson, Hans P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 35, 29.08.2017, p. E7367-E7376.

Research output: Contribution to journalArticle

Barro, Rene ; Ramentol, Rosamary ; Liin, Sara I. ; Perez, Marta E. ; Kass, Robert S. ; Larsson, Hans P. / KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 35. pp. E7367-E7376.
@article{c778bfefc5934595bd1f583937d579e2,
title = "KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions",
abstract = "KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coas-sembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphos-phate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.",
keywords = "KCNE1, KCNE3, KCNQ1, Kv7.1, Voltage clamp fluorometry",
author = "Rene Barro and Rosamary Ramentol and Liin, {Sara I.} and Perez, {Marta E.} and Kass, {Robert S.} and Larsson, {Hans P}",
year = "2017",
month = "8",
day = "29",
doi = "10.1073/pnas.1710335114",
language = "English (US)",
volume = "114",
pages = "E7367--E7376",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "35",

}

TY - JOUR

T1 - KCNE1 and KCNE3 modulate KCNQ1 channels by affecting different gating transitions

AU - Barro, Rene

AU - Ramentol, Rosamary

AU - Liin, Sara I.

AU - Perez, Marta E.

AU - Kass, Robert S.

AU - Larsson, Hans P

PY - 2017/8/29

Y1 - 2017/8/29

N2 - KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coas-sembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphos-phate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.

AB - KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the heart, KCNE1 associates with the α-subunit KCNQ1 to generate the slowly activating, voltage-dependent potassium current (IKs) in the heart that controls the repolarization phase of cardiac action potentials. By contrast, in epithelial cells from the colon, stomach, and kidney, KCNE3 coas-sembles with KCNQ1 to form K+ channels that are voltage-independent K+ channels in the physiological voltage range and important for controlling water and salt secretion and absorption. How KCNE1 and KCNE3 subunits modify KCNQ1 channel gating so differently is largely unknown. Here, we use voltage clamp fluorometry to determine how KCNE1 and KCNE3 affect the voltage sensor and the gate of KCNQ1. By separating S4 movement and gate opening by mutations or phosphatidylinositol 4,5-bisphos-phate depletion, we show that KCNE1 affects both the S4 movement and the gate, whereas KCNE3 affects the S4 movement and only affects the gate in KCNQ1 if an intact S4-to-gate coupling is present. Further, we show that a triple mutation in the middle of the transmembrane (TM) segment of KCNE3 introduces KCNE1-like effects on the second S4 movement and the gate. In addition, we show that differences in two residues at the external end of the KCNE TM segments underlie differences in the effects of the different KCNEs on the first S4 movement and the voltage sensor-to-gate coupling.

KW - KCNE1

KW - KCNE3

KW - KCNQ1

KW - Kv7.1

KW - Voltage clamp fluorometry

UR - http://www.scopus.com/inward/record.url?scp=85028542155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028542155&partnerID=8YFLogxK

U2 - 10.1073/pnas.1710335114

DO - 10.1073/pnas.1710335114

M3 - Article

VL - 114

SP - E7367-E7376

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 35

ER -