PortalPublikationenMechanism of external K+ sensitivity of KCNQ1 channels

Mechanism of external K+ sensitivity of KCNQ1 channels

Standard

Mechanism of external K+ sensitivity of KCNQ1 channels. / Abrahamyan, Astghik; Eldstrom, Jodene; Sahakyan, Harutyun; Karagulyan, Nare; Mkrtchyan, Liana; Karapetyan, Tatev; Sargsyan, Ernest; Kneussel, Matthias; Nazaryan, Karen; Schwarz, Jürgen R; Fedida, David; Vardanyan, Vitya.

in: J GEN PHYSIOL, Jahrgang 155, Nr. 5, 01.05.2023, S. e202213205.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Abrahamyan, A, Eldstrom, J, Sahakyan, H, Karagulyan, N, Mkrtchyan, L, Karapetyan, T, Sargsyan, E, Kneussel, M, Nazaryan, K, Schwarz, JR, Fedida, D & Vardanyan, V 2023, 'Mechanism of external K+ sensitivity of KCNQ1 channels', J GEN PHYSIOL, Jg. 155, Nr. 5, S. e202213205. https://doi.org/10.1085/jgp.202213205

APA

Abrahamyan, A., Eldstrom, J., Sahakyan, H., Karagulyan, N., Mkrtchyan, L., Karapetyan, T., Sargsyan, E., Kneussel, M., Nazaryan, K., Schwarz, J. R., Fedida, D., & Vardanyan, V. (2023). Mechanism of external K+ sensitivity of KCNQ1 channels. J GEN PHYSIOL, 155(5), e202213205. https://doi.org/10.1085/jgp.202213205

Vancouver

Abrahamyan A, Eldstrom J, Sahakyan H, Karagulyan N, Mkrtchyan L, Karapetyan T et al. Mechanism of external K+ sensitivity of KCNQ1 channels. J GEN PHYSIOL. 2023 Mai 1;155(5):e202213205. https://doi.org/10.1085/jgp.202213205

Bibtex

@article{429873aada3343359f326a8746574715,
title = "Mechanism of external K+ sensitivity of KCNQ1 channels",
abstract = "KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+. First, we demonstrate the involvement of the selectivity filter in the external K+ sensitivity of the channel. Then, we show that external K+ binds to the vacant outermost ion coordination site of the selectivity filter inducing a diminution in the unitary conductance of the channel. The larger reduction in the unitary conductance compared to whole-cell currents suggests an additional modulatory effect of external K+ on the channel. Further, we show that the external K+ sensitivity of the heteromeric KCNQ1/KCNE complexes depends on the type of associated KCNE subunits.",
keywords = "KCNQ1 Potassium Channel/metabolism, Potassium Channels, Voltage-Gated/metabolism, Molecular Dynamics Simulation, Oocytes/metabolism, Patch-Clamp Techniques",
author = "Astghik Abrahamyan and Jodene Eldstrom and Harutyun Sahakyan and Nare Karagulyan and Liana Mkrtchyan and Tatev Karapetyan and Ernest Sargsyan and Matthias Kneussel and Karen Nazaryan and Schwarz, {J{\"u}rgen R} and David Fedida and Vitya Vardanyan",
note = "{\textcopyright} 2023 Abrahamyan et al.",
year = "2023",
month = may,
day = "1",
doi = "10.1085/jgp.202213205",
language = "English",
volume = "155",
pages = "e202213205",
journal = "J GEN PHYSIOL",
issn = "0022-1295",
publisher = "Rockefeller University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Mechanism of external K+ sensitivity of KCNQ1 channels

AU - Abrahamyan, Astghik

AU - Eldstrom, Jodene

AU - Sahakyan, Harutyun

AU - Karagulyan, Nare

AU - Mkrtchyan, Liana

AU - Karapetyan, Tatev

AU - Sargsyan, Ernest

AU - Kneussel, Matthias

AU - Nazaryan, Karen

AU - Schwarz, Jürgen R

AU - Fedida, David

AU - Vardanyan, Vitya

N1 - © 2023 Abrahamyan et al.

PY - 2023/5/1

Y1 - 2023/5/1

N2 - KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+. First, we demonstrate the involvement of the selectivity filter in the external K+ sensitivity of the channel. Then, we show that external K+ binds to the vacant outermost ion coordination site of the selectivity filter inducing a diminution in the unitary conductance of the channel. The larger reduction in the unitary conductance compared to whole-cell currents suggests an additional modulatory effect of external K+ on the channel. Further, we show that the external K+ sensitivity of the heteromeric KCNQ1/KCNE complexes depends on the type of associated KCNE subunits.

AB - KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+. First, we demonstrate the involvement of the selectivity filter in the external K+ sensitivity of the channel. Then, we show that external K+ binds to the vacant outermost ion coordination site of the selectivity filter inducing a diminution in the unitary conductance of the channel. The larger reduction in the unitary conductance compared to whole-cell currents suggests an additional modulatory effect of external K+ on the channel. Further, we show that the external K+ sensitivity of the heteromeric KCNQ1/KCNE complexes depends on the type of associated KCNE subunits.

KW - KCNQ1 Potassium Channel/metabolism

KW - Potassium Channels, Voltage-Gated/metabolism

KW - Molecular Dynamics Simulation

KW - Oocytes/metabolism

KW - Patch-Clamp Techniques

U2 - 10.1085/jgp.202213205

DO - 10.1085/jgp.202213205

M3 - SCORING: Journal article

C2 - 36809486

VL - 155

SP - e202213205

JO - J GEN PHYSIOL

JF - J GEN PHYSIOL

SN - 0022-1295

IS - 5

ER -