Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel. / Liin, Sara I.; Silverå Ejneby, Malin; Barro-Soria, Rene; Skarsfeldt, Mark Alexander; Larsson, Johan E.; Starck Härlin, Frida; Parkkari, Teija; Bentzen, Bo Hjorth; Schmitt, Nicole; Larsson, H. Peter; Elinder, Fredrik.

In: Proceedings of the National Academy of Science of the United States of America, Vol. 112, No. 18, 05.05.2015, p. 5714–5719.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Liin, SI, Silverå Ejneby, M, Barro-Soria, R, Skarsfeldt, MA, Larsson, JE, Starck Härlin, F, Parkkari, T, Bentzen, BH, Schmitt, N, Larsson, HP & Elinder, F 2015, 'Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel', Proceedings of the National Academy of Science of the United States of America, vol. 112, no. 18, pp. 5714–5719. https://doi.org/10.1073/pnas.1503488112

APA

Liin, S. I., Silverå Ejneby, M., Barro-Soria, R., Skarsfeldt, M. A., Larsson, J. E., Starck Härlin, F., Parkkari, T., Bentzen, B. H., Schmitt, N., Larsson, H. P., & Elinder, F. (2015). Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel. Proceedings of the National Academy of Science of the United States of America, 112(18), 5714–5719. https://doi.org/10.1073/pnas.1503488112

Vancouver

Liin SI, Silverå Ejneby M, Barro-Soria R, Skarsfeldt MA, Larsson JE, Starck Härlin F et al. Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel. Proceedings of the National Academy of Science of the United States of America. 2015 May 5;112(18):5714–5719. https://doi.org/10.1073/pnas.1503488112

Author

Liin, Sara I. ; Silverå Ejneby, Malin ; Barro-Soria, Rene ; Skarsfeldt, Mark Alexander ; Larsson, Johan E. ; Starck Härlin, Frida ; Parkkari, Teija ; Bentzen, Bo Hjorth ; Schmitt, Nicole ; Larsson, H. Peter ; Elinder, Fredrik. / Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel. In: Proceedings of the National Academy of Science of the United States of America. 2015 ; Vol. 112, No. 18. pp. 5714–5719.

Bibtex

@article{f74d8785e35d4e409f038c934215facc,
title = "Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel",
abstract = "Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.",
author = "Liin, {Sara I.} and {Silver{\aa} Ejneby}, Malin and Rene Barro-Soria and Skarsfeldt, {Mark Alexander} and Larsson, {Johan E.} and {Starck H{\"a}rlin}, Frida and Teija Parkkari and Bentzen, {Bo Hjorth} and Nicole Schmitt and Larsson, {H. Peter} and Fredrik Elinder",
year = "2015",
month = may,
day = "5",
doi = "10.1073/pnas.1503488112",
language = "English",
volume = "112",
pages = "5714–5719",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "18",

}

RIS

TY - JOUR

T1 - Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel

AU - Liin, Sara I.

AU - Silverå Ejneby, Malin

AU - Barro-Soria, Rene

AU - Skarsfeldt, Mark Alexander

AU - Larsson, Johan E.

AU - Starck Härlin, Frida

AU - Parkkari, Teija

AU - Bentzen, Bo Hjorth

AU - Schmitt, Nicole

AU - Larsson, H. Peter

AU - Elinder, Fredrik

PY - 2015/5/5

Y1 - 2015/5/5

N2 - Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.

AB - Polyunsaturated fatty acids (PUFAs) affect cardiac excitability. Kv7.1 and the β-subunit KCNE1 form the cardiac IKs channel that is central for cardiac repolarization. In this study, we explore the prospects of PUFAs as IKs channel modulators. We report that PUFAs open Kv7.1 via an electrostatic mechanism. Both the polyunsaturated acyl tail and the negatively charged carboxyl head group are required for PUFAs to open Kv7.1. We further show that KCNE1 coexpression abolishes the PUFA effect on Kv7.1 by promoting PUFA protonation. PUFA analogs with a decreased pKa value, to preserve their negative charge at neutral pH, restore the sensitivity to open IKs channels. PUFA analogs with a positively charged head group inhibit IKs channels. These different PUFA analogs could be developed into drugs to treat cardiac arrhythmias. In support of this possibility, we show that PUFA analogs act antiarrhythmically in embryonic rat cardiomyocytes and in isolated perfused hearts from guinea pig.

U2 - 10.1073/pnas.1503488112

DO - 10.1073/pnas.1503488112

M3 - Journal article

C2 - 25901329

VL - 112

SP - 5714

EP - 5719

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 - 18

ER -

ID: 136252750