KCNE3 acts by promoting voltage sensor activation in KCNQ1

Rene Barro, Marta E. Perez, Hans P Larsson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K+ channels important for K+ and Cl- secretion that appear to be voltageindependent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.

Original languageEnglish (US)
Pages (from-to)E7286-E7292
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number52
DOIs
StatePublished - Dec 29 2015

Fingerprint

R-228
Voltage-Gated Potassium Channels
Fluorometry
Static Electricity
Stomach
Colon
Kidney
Mutation

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

KCNE3 acts by promoting voltage sensor activation in KCNQ1. / Barro, Rene; Perez, Marta E.; Larsson, Hans P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 52, 29.12.2015, p. E7286-E7292.

Research output: Contribution to journalArticle

@article{b5f430c56c634145b0fc5f6816ad6ea1,
title = "KCNE3 acts by promoting voltage sensor activation in KCNQ1",
abstract = "KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K+ channels important for K+ and Cl- secretion that appear to be voltageindependent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.",
keywords = "KCNE3, KCNQ1, Kv7.1, Voltage clamp fluorometry, Voltage sensor",
author = "Rene Barro and Perez, {Marta E.} and Larsson, {Hans P}",
year = "2015",
month = "12",
day = "29",
doi = "10.1073/pnas.1516238112",
language = "English (US)",
volume = "112",
pages = "E7286--E7292",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "52",

}

TY - JOUR

T1 - KCNE3 acts by promoting voltage sensor activation in KCNQ1

AU - Barro, Rene

AU - Perez, Marta E.

AU - Larsson, Hans P

PY - 2015/12/29

Y1 - 2015/12/29

N2 - KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K+ channels important for K+ and Cl- secretion that appear to be voltageindependent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.

AB - KCNE β-subunits assemble with and modulate the properties of voltage-gated K+ channels. In the colon, stomach, and kidney, KCNE3 coassembles with the α-subunit KCNQ1 to form K+ channels important for K+ and Cl- secretion that appear to be voltageindependent. How KCNE3 subunits turn voltage-gated KCNQ1 channels into apparent voltage-independent KCNQ1/KCNE3 channels is not completely understood. Different mechanisms have been proposed to explain the effect of KCNE3 on KCNQ1 channels. Here, we use voltage clamp fluorometry to determine how KCNE3 affects the voltage sensor S4 and the gate of KCNQ1. We find that S4 moves in KCNQ1/KCNE3 channels, and that inward S4 movement closes the channel gate. However, KCNE3 shifts the voltage dependence of S4 movement to extreme hyperpolarized potentials, such that in the physiological voltage range, the channel is constitutively conducting. By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Two negatively charged residues of KCNE3 (D54 and D55) are found essential for the effect of KCNE3 on KCNQ1 channels, mainly exerting their effects by an electrostatic interaction with R228 in S4. Our results suggest that KCNE3 primarily affects the voltage-sensing domain and only indirectly affects the gate.

KW - KCNE3

KW - KCNQ1

KW - Kv7.1

KW - Voltage clamp fluorometry

KW - Voltage sensor

UR - http://www.scopus.com/inward/record.url?scp=84952683510&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952683510&partnerID=8YFLogxK

U2 - 10.1073/pnas.1516238112

DO - 10.1073/pnas.1516238112

M3 - Article

VL - 112

SP - E7286-E7292

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 - 52

ER -