KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate

Jeremiah D. Osteen, Carlos Gonzalez, Kevin J. Sampson, Vivek Iyer, Santiago Rebolledo, Hans P Larsson, Robert S. Kass

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The delayed rectifier IKs potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native IKs channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the IKs channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.

Original languageEnglish
Pages (from-to)22710-22715
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number52
DOIs
StatePublished - Dec 28 2010

Fingerprint

Intermediate-Conductance Calcium-Activated Potassium Channels
Delayed Rectifier Potassium Channels
Fluorescence
Fluorometry
Ion Channels
Proteins

ASJC Scopus subject areas

  • General

Cite this

KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate. / Osteen, Jeremiah D.; Gonzalez, Carlos; Sampson, Kevin J.; Iyer, Vivek; Rebolledo, Santiago; Larsson, Hans P; Kass, Robert S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 52, 28.12.2010, p. 22710-22715.

Research output: Contribution to journalArticle

Osteen, Jeremiah D. ; Gonzalez, Carlos ; Sampson, Kevin J. ; Iyer, Vivek ; Rebolledo, Santiago ; Larsson, Hans P ; Kass, Robert S. / KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 52. pp. 22710-22715.
@article{1b5dd59a6851464d8fa05bb14ce18fee,
title = "KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate",
abstract = "The delayed rectifier IKs potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native IKs channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the IKs channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.",
author = "Osteen, {Jeremiah D.} and Carlos Gonzalez and Sampson, {Kevin J.} and Vivek Iyer and Santiago Rebolledo and Larsson, {Hans P} and Kass, {Robert S.}",
year = "2010",
month = "12",
day = "28",
doi = "10.1073/pnas.1016300108",
language = "English",
volume = "107",
pages = "22710--22715",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "52",

}

TY - JOUR

T1 - KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate

AU - Osteen, Jeremiah D.

AU - Gonzalez, Carlos

AU - Sampson, Kevin J.

AU - Iyer, Vivek

AU - Rebolledo, Santiago

AU - Larsson, Hans P

AU - Kass, Robert S.

PY - 2010/12/28

Y1 - 2010/12/28

N2 - The delayed rectifier IKs potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native IKs channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the IKs channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.

AB - The delayed rectifier IKs potassium channel, formed by coassembly of α- (KCNQ1) and β- (KCNE1) subunits, is essential for cardiac function. Although KCNE1 is necessary to reproduce the functional properties of the native IKs channel, the mechanism(s) through which KCNE1 modulates KCNQ1 is unknown. Here we report measurements of voltage sensor movements in KCNQ1 and KCNQ1/KCNE1 channels using voltage clamp fluorometry. KCNQ1 channels exhibit indistinguishable voltage dependence of fluorescence and current signals, suggesting a one-to-one relationship between voltage sensor movement and channel opening. KCNE1 coexpression dramatically separates the voltage dependence of KCNQ1/KCNE1 current and fluorescence, suggesting an imposed requirement for movements of multiple voltage sensors before KCNQ1/KCNE1 channel opening. This work provides insight into the mechanism by which KCNE1 modulates the IKs channel and presents a mechanism for distinct β-subunit regulation of ion channel proteins.

UR - http://www.scopus.com/inward/record.url?scp=78651087721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651087721&partnerID=8YFLogxK

U2 - 10.1073/pnas.1016300108

DO - 10.1073/pnas.1016300108

M3 - Article

C2 - 21149716

AN - SCOPUS:78651087721

VL - 107

SP - 22710

EP - 22715

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 -