IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36730-7.html
   My bibliography  Save this article

Noncanonical electromechanical coupling paths in cardiac hERG potassium channel

Author

Listed:
  • Carlos A. Z. Bassetto

    (The University of Chicago)

  • Flavio Costa

    (Sapienza Università di Roma)

  • Carlo Guardiani

    (Sapienza Università di Roma)

  • Francisco Bezanilla

    (The University of Chicago
    The University of Chicago
    Universidad de Valparaiso)

  • Alberto Giacomello

    (Sapienza Università di Roma)

Abstract

Voltage-gated potassium channels are involved in many physiological processes such as nerve impulse transmission, the heartbeat, and muscle contraction. However, for many of them the molecular determinants of the gating mechanism remain elusive. Here, using a combination of theoretical and experimental approaches, we address this problem focusing on the cardiac hERG potassium channel. Network analysis of molecular dynamics trajectories reveals the presence of a kinematic chain of residues that couples the voltage sensor domain to the pore domain and involves the S4/S1 and S1/S5 subunit interfaces. Mutagenesis experiments confirm the role of these residues and interfaces in the activation and inactivation mechanisms. Our findings demonstrate the presence of an electromechanical transduction path crucial for the non-domain-swapped hERG channel gating that resembles the noncanonical path identified in domain-swapped K+ channels.

Suggested Citation

  • Carlos A. Z. Bassetto & Flavio Costa & Carlo Guardiani & Francisco Bezanilla & Alberto Giacomello, 2023. "Noncanonical electromechanical coupling paths in cardiac hERG potassium channel," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36730-7
    DOI: 10.1038/s41467-023-36730-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36730-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36730-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. João L. Carvalho-de-Souza & Francisco Bezanilla, 2019. "Noncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of Shaker," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Xiao Tao & Richard K. Hite & Roderick MacKinnon, 2017. "Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel," Nature, Nature, vol. 541(7635), pages 46-51, January.
    3. Michael David Clark & Gustavo F. Contreras & Rong Shen & Eduardo Perozo, 2020. "Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1," Nature, Nature, vol. 583(7814), pages 145-149, July.
    4. Michael C. Sanguinetti & Martin Tristani-Firouzi, 2006. "hERG potassium channels and cardiac arrhythmia," Nature, Nature, vol. 440(7083), pages 463-469, March.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Gonçalo Paulo & Ke Sun & Giovanni Di Muccio & Alberto Gubbiotti & Blasco Morozzo della Rocca & Jia Geng & Giovanni Maglia & Mauro Chinappi & Alberto Giacomello, 2023. "Hydrophobically gated memristive nanopores for neuromorphic applications," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Amrita X Sarkar & Eric A Sobie, 2010. "Regression Analysis for Constraining Free Parameters in Electrophysiological Models of Cardiac Cells," PLOS Computational Biology, Public Library of Science, vol. 6(9), pages 1-11, September.
    2. Qiansheng Liang & Gamma Chi & Leonardo Cirqueira & Lianteng Zhi & Agostino Marasco & Nadia Pilati & Martin J. Gunthorpe & Giuseppe Alvaro & Charles H. Large & David B. Sauer & Werner Treptow & Manuel , 2024. "The binding and mechanism of a positive allosteric modulator of Kv3 channels," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Tobias Raisch & Andreas Brockmann & Ulrich Ebbinghaus-Kintscher & Jörg Freigang & Oliver Gutbrod & Jan Kubicek & Barbara Maertens & Oliver Hofnagel & Stefan Raunser, 2021. "Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Guohui Zhang & Xianjin Xu & Zhiguang Jia & Yanyan Geng & Hongwu Liang & Jingyi Shi & Martina Marras & Carlota Abella & Karl L. Magleby & Jonathan R. Silva & Jianhan Chen & Xiaoqin Zou & Jianmin Cui, 2022. "An allosteric modulator activates BK channels by perturbing coupling between Ca2+ binding and pore opening," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Fang Du & Joseph J Babcock & Haibo Yu & Beiyan Zou & Min Li, 2015. "Global Analysis Reveals Families of Chemical Motifs Enriched for hERG Inhibitors," PLOS ONE, Public Library of Science, vol. 10(2), pages 1-21, February.
    6. Joshua Mayourian & Ruben M Savizky & Eric A Sobie & Kevin D Costa, 2016. "Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes," PLOS Computational Biology, Public Library of Science, vol. 12(7), pages 1-29, July.
    7. Mingfeng Zhang & Yuanyue Shan & Duanqing Pei, 2023. "Mechanism underlying delayed rectifying in human voltage-mediated activation Eag2 channel," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Bryan Cernuda & Christopher Thomas Fernandes & Salma Mohamed Allam & Matthew Orzillo & Gabrielle Suppa & Zuleen Chia Chang & Demosthenes Athanasopoulos & Zafir Buraei, 2019. "The molecular determinants of R-roscovitine block of hERG channels," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-26, September.
    9. Yaming Lu & Miao Yu & Yutian Jia & Fan Yang & Yanming Zhang & Xia Xu & Xiaomin Li & Fan Yang & Jianlin Lei & Yi Wang & Guanghui Yang, 2022. "Structural basis for the activity regulation of a potassium channel AKT1 from Arabidopsis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Haiyan Mao & Xiaoli Lu & Justin Michael Karush & Xiaoyan Huang & Xi Yang & Yanna Ba & Ying Wang & Ningsheng Liu & Jianqing Zhou & Jiangfang Lian, 2013. "Pharmacologic Approach to Defective Protein Trafficking in the E637K-hERG Mutant with PD-118057 and Thapsigargin," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-12, June.
    11. Moniruzzaman & Mohammed Jabedul Hoque & Amrin Ahsan & Md Belayet Hossain, 2018. "Molecular Docking, Pharmacokinetic, and DFT Calculation of Naproxen and its Degradants," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 9(5), pages 7360-7365, October.
    12. Dahai Yu & Lin Lv & Li Fang & Bo Zhang & Junnan Wang & Ge Zhan & Lei Zhao & Xin Zhao & Baoxin Li, 2017. "Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-19, August.
    13. Moniruzzaman & Mohammed Jabedul Hoque & Mohammad Nasir Uddin & Amrin Ahsan & Tareq Mahmud, 2018. "Quantum Chemical, Molecular Docking, and ADMET Predictions of Ketorolac and its Modified Analogues," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 11(5), pages 8723-8729, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36730-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.