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Molecular mechanisms of activation and modulation of recombinant GABAA receptors by selected agonists and modulators

2013/11/B/NZ3/00983

Keywords

Descriptors

  • NZ3_6: Neurobiologia komórkowa
  • NZ3_7: Przekaźnictwo sygnału
  • NZ3_5: Neurobiologia molekularna

Panel

NZ3 – Cellular and developmental biology: cell biology, developmental biology, ageing biology, neurobiology

Host institution

Uniwersytet Medyczny im. Piastów Śląskich we Wrocławiu, Wydział Farmaceutyczny z Oddziałem Analiutyki Medycznej, Wydział Lekarski

Voivodeship: dolnośląskie

Other projects carried out by the institution »

Principal investigator (from the host institution)

prof. Jerzy Władysław Mozrzymas

Number of co-investigators in the project: 5

Call

OPUS 6 – announced on 2013-09-16

Amount awarded
563 960 PLN
Project start date
2014-08-07
Project end date
2018-08-06
Project duration
48 months (the same as in the proposal)
Project status
Project settled

Equipment purchased [PL]

  1. Niskoszumowy wzmacniacz do pomiarów elektrofizjologicznych Axopatch 200B, Molecular Devices. Cost: 67 000 PLN
  2. Przetwornik analogowo-cyfrowy Digidata 1550, Molecular Devices. Cost: 43 000 PLN

Information in the final report

Publication in academic press/journals (4)

  1. Spontaneous activity, singly bound states and the impact of alpha1Phe64 mutation on GABAAR gating in the novel kinetic model based on the single-channel recordings

    Authors:
    Magdalena Kisiel, Magdalena Jatczak, Marek Brodzki, Jerzy W. Mozrzymas
    Academic press:
    Neuropharmacology (year: 2018, volume: 131, pages: 453-474), Publisher: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.neuropharm.2017.11.030 – link to the publication

  2. Comparison of kinetic and pharmacological profiles of recombinant α1γ2L and α1β2γ2L GABAA receptors - A clue to the role of intersubunit interactions

    Authors:
    Brodzki M, Rutkowski R, Jatczak M, Kisiel M, Czyzewska MM, Mozrzymas JW
    Academic press:
    European Journal of Pharmacology (year: 2016, volume: 784, pages: 81-89), Publisher: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.ejphar.2016.05.015 – link to the publication

  3. Protons modulate gating of recombinant α1β2γ2 GABAA receptor by affecting desensitization and opening transitions

    Authors:
    Magdalena Kisiel, Magdalena Jatczak-Śliwa, Jerzy W Mozrzymas
    Academic press:
    Neuropharmacology (year: 2019, volume: 146, pages: 300-315), Publisher: Elsevier
    Status:
    Published
    DOI:
    10.1016/j.neuropharm.2018.10.016 – link to the publication

  4. Distinct modulation of spontaneous and GABA-evoked gating by flurazepam shapes cross-talk between agonist-free and liganded GABAA receptor activity

    Authors:
    Magdalena Jatczak-Śliwa, Katarzyna Terejko, Marek Brodzki, Michał Adam Michałowski, Marta Magdalena Czyzewska, Joanna Maria Nowicka, Anna Andrzejczak, Rakenduvadhana Srinivasan, Jerzy W. Mozrzymas
    Academic press:
    Frontiers in Cellular Neuroscience (year: 2018, volume: 12, pages: 237), Publisher: Frontiers Media
    Status:
    Published
    DOI:
    10.3389/fncel.2018.00237 – link to the publication

Articles in post-conference publications (28)

  1. Muscimol-evoked currents are profoundly altered by agonist binding site mutation β2E155C in α1β2γ2L and α1β2 GABAA receptors

    Authors:
    Marta M. Czyżewska, Magdalena Kisiel, Magdalena Jatczak, Marek Brodzki, Jerzy W. Mozrzymas
    Conference:
    NEURONUS 2016 IBRO & IRUN Neuroscience Forum (year: 2016, pages: 51), Publisher: www.neuronusforum.pl
    Date:
    conference 22 - 24 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  2. Mutation at the binding site β2E155 residue affects both binding and gating properties of α1β2γ2 GABAA receptors

    Authors:
    Magdalena Jatczak, Magdalena Kisiel, Marta M. Czyżewska, Marek Brodzki, Cynthia Czajkowski, Jerzy W. Mozrzymas
    Conference:
    NEURONUS 2016 IBRO & IRUN Neuroscience Forum (year: 2016, pages: 47), Publisher: www.neuronusforum.pl
    Date:
    conference 22 - 24 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  3. Involvement of key binding site residues of GABAA receptor in full and partial agonist binding

    Authors:
    Michał Adam Michałowski, Jerzy W. Mozrzymas
    Conference:
    NEURONUS 2016 IBRO & IRUN Neuroscience Forum (year: 2016, pages: 44), Publisher: www.neuronusforum.pl
    Date:
    conference 22 - 24 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  4. Modulacja aktywności receptora GABAA przez flurazepam

    Authors:
    Jatczak-Śliwa M, Terejko K, Brodzki M, Michałowski MA, Czyzewska MM, Nowicka JM, Andrzejczak A, Rakenduvadhana S, Mozrzymas JW
    Conference:
    IX Sympozjum Współczesna Myśl Techniczna w Naukach Medycznych i Biologicznych (year: 2018, pages: 28, 29), Publisher: Polska Akademia Nauk Oddział we Wrocławiu
    Date:
    conference 22-23.06
    Status:
    Published

  5. Alpha1-gamma2 and alpha1-beta2-gamma2 GABA(A) receptors show distinct pharmacological characteristics

    Authors:
    Brodzki M., Czyżewska M.M., Rutkowski R., Kisiel M., Jatczak M., Mozrzymas J.W.
    Conference:
    NEURONUS IBRO & IRUN Neuroscience Forum 2015, (year: 2015, pages: 76), Publisher: www.neuronusforum.pl
    Date:
    conference 17-19 kwietnia
    Status:
    Published

  6. Protons modulate GABAA receptor gating by affecting both desensitization and flipping transitions

    Authors:
    Magdalena Kisiel, Magdalena Jatczak, Jerzy W. Mozrzymas
    Conference:
    NEURONUS 2015 IBRO & IRUN Neuroscience Forum (year: 2015, pages: 75), Publisher: www.neuronusforum.pl
    Date:
    conference 17-18 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  7. Mutation of glutamate 155 residue in the β2 subunit of the α1β2γ2 GABA receptor alters both binding and gating and is likely to be involved in preactivation/flipping mechanism

    Authors:
    Magdalena E. Jatczak, Magdalena Kisiel, Marta M. Czyżewska, Marek Brodzki, Jerzy W. Mozrzymas
    Conference:
    NEURONUS 2015 IBRO & IRUN Neuroscience Forum (year: 2015, pages: 75), Publisher: www.neuronusforum.pl
    Date:
    conference 17-18 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  8. GABAA receptor binding site residue beta2 glutamate155: possible role in channel preactivation

    Authors:
    Magdalena Kisiel, Magdalena Jatczak, Marta M. Czyżewska, Marek Brodzki, Cynthia Czajkowski, Jerzy W. Mozrzymas
    Conference:
    12th International Congress of the Polish Neuroscience Society (year: 2015, pages: S51), Publisher: Acta Neurobiologiae Experimentalis, Vol. 75 (2015) Supplement
    Date:
    conference 6-8 września
    Status:
    Published
    DOI:
    link to the publication

  9. Protons affect GABAA receptor gating by altering both preactivation and desensitization transitions.

    Authors:
    Magdalena Kisiel, Magdalena Jatczak, Jerzy W. Mozrzymas
    Conference:
    12th International Congress of the Polish Neuroscience Society (year: 2015, pages: S108), Publisher: Acta Neurobiologiae Experimentalis, Vol. 75 (2015) Supplement
    Date:
    conference 6-8 września
    Status:
    Published
    DOI:
    link to the publication

  10. Different pharmacological profile in α1-γ2L and α1-β2-γ2L GABA(A) receptors

    Authors:
    Brodzki M., Czyżewska M.M., Rutkowski R., Kisiel M., Jatczak M., Mozrzymas J.W.
    Conference:
    12th International Congress of the Polish Neuroscience Society (year: 2015, pages: S46), Publisher: Acta Neurobiologiae Experimentalis, Vol. 75 (2015) Supplement
    Date:
    conference 6-8 września
    Status:
    Published
    DOI:
    link to the publication

  11. Linking agonist binding to GABAa receptor opening transition

    Authors:
    Jerzy W. Mozrzymas, Magdalena Kisiel, Magdalena Jatczak, Marta Czyżewska, Marek Brodzki
    Conference:
    12th International Congress of the Polish Neuroscience Society (year: 2015, pages: S31), Publisher: Acta Neurobiologiae Experimentalis, Vol. 75 (2015) Supplement
    Date:
    conference 6-8 września
    Status:
    Published
    DOI:
    link to the publication

  12. Modulation of GABAA receptor (α1 β2 γ2) gating by protons involves changes in flipping transitions.

    Authors:
    J.W. Mozrzymas, M. Kisiel, M. Jatczak
    Conference:
    42nd Annual Meeting of the Society for Neuroscience (year: 2014, pages: program no.124.20/B35), Publisher: Society for Neuroscience
    Date:
    conference 15-19 listopada
    Status:
    Published
    DOI:
    link to the publication

  13. PROTONS DIFFERENTLY MODULATE MACROSCOPIC CURRENTS EVOKED IN WILD TYPE α1β2γ2 GABAA RECEPTORS AND IN α1F64 MUTANTS

    Authors:
    Jatczak M, Kisiel M, Mozrzymas JW
    Conference:
    10th Conference on Electrophysiological Techniques in Bioelectricity Research: from Ion Channels to Neural Networks (year: 2016, pages: 3), Publisher: www.neuro.iz.uj.edu.pl
    Date:
    conference 3 - 4 czerwca
    Status:
    Published
    DOI:
    link to the publication

  14. Wpływ mutacji β2E155 w obrębie miejsca wiążącego agonistę w receptorze GABAA na mechanizm działania tego receptora

    Authors:
    Magdalena Jatczak, Magdalena Kisiel, Marta M. Czyżewska, Marek Brodzki, Jerzy W. Mozrzymas
    Conference:
    VI Sympozjum Współczesna Myśl Techniczna w Naukach Medycznych i Biologicznych (year: 2015, pages: 41-42), Publisher: Oddział Polskiej Akademii Nauk we Wrocławiu
    Date:
    conference 19-20 czerwca
    Status:
    Published
    DOI:
    link to the publication

  15. CHARAKTERYSTYKA FARMAKOLOGICZNA I KINETYCZNA REKOMBINOWANYCH RECEPTORÓW GABA(A) PODTYPÓW α1γ2L I α1β2γ2L JAKO PRZESŁANKA O FUNKCJONALNEJ ROLI INTERAKCJI MIĘDZYPODJEDNOSTKOWYCH

    Authors:
    Marek Brodzki, Radosław Rutkowski, Magdalena Jatczak, Magdalena Kisiel, Marta M. Czyżewska, Jerzy W. Mozrzymas
    Conference:
    VII Sympozjum Współczesna Myśl Techniczna w Naukach Medycznych i Biologicznych (year: 2016, pages: 3), Publisher: http://www.7sympkib.pwr.edu.pl
    Date:
    conference 25 - 26 czerwca
    Status:
    Published

  16. Porównanie właściwości kinetycznych i farmakologicznych podtypów α1- γ2L i α1-β2-γ2L rekombinowanych receptorów GABA(A)

    Authors:
    Brodzki M., Czyżewska M.M., Rutkowski R., Kisiel M., Jatczak M., Mozrzymas J.W.
    Conference:
    VI Sympozjum Współczesna Myśl Techniczna w Naukach Medycznych i Biologicznych (year: 2015, pages: 15-16), Publisher: Oddział Polskiej Akademii Nauk we Wrocławiu
    Date:
    conference 19-20 czerwca
    Status:
    Published
    DOI:
    link to the publication

  17. WPŁYW MUTACJI MIEJSCA WIĄŻĄCEGO DLA AGONISTY W RECEPTORZE GABAA (α1F64) NA MODULACJĘ TEGO RECEPTORA PRZEZ ODCZYN ŚRODOWISKA ZEWNĄTRZKOMÓRKOWEGO

    Authors:
    Magdalena Jatczak, Magdalena Kisiel, Jerzy W. Mozrzymas
    Conference:
    VII Sympozjum Współczesna Myśl Techniczna w Naukach Medycznych i Biologicznych (year: 2016, pages: 4), Publisher: www.7sympkib.pwr.edu.pl
    Date:
    conference 24 - 25 czerwca
    Status:
    Published

  18. Intersubunit interactions of heteropentamer GABAA receptor compared to crystal structures of homopentamer cys-loop family receptors

    Authors:
    Michałowski MA, Mozrzymas JW
    Conference:
    10th Conference on Electrophysiological Techniques in Bioelectricity Research: from Ion Channels to Neural Networks (year: 2016, pages: 4), Publisher: www.neuro.iz.uj.edu.pl
    Date:
    conference 3 - 4 czerwca
    Status:
    Published
    DOI:
    link to the publication

  19. AGONIST BINDING SITE MUTATION β2E155C AFFECTS BOTH BINDING AND GATING TRANSITIONS DURING GABAA RECEPTOR ACTIVATION

    Authors:
    Czyżewska MM, Kisiel M, Jatczak M, Brodzki M, Mozrzymas JW
    Conference:
    10th Conference on Electrophysiological Techniques in Bioelectricity Research: from Ion Channels to Neural Networks (year: 2016, pages: 4), Publisher: www.neuro.iz.uj.edu.pl
    Date:
    conference 3 - 4 czerwca
    Status:
    Published
    DOI:
    link to the publication

  20. SINGLE-CHANNEL RECORDINGS REVEAL THE MECHANISM OF PH MODULATION OF GABAA RECEPTOR ACTIVATION

    Authors:
    Kisiel M, Jatczak M, Mozrzymas JW
    Conference:
    10th Conference on Electrophysiological Techniques in Bioelectricity Research: from Ion Channels to Neural Networks (year: 2016, pages: 4), Publisher: www.neuro.iz.uj.edu.pl
    Date:
    conference 3 - 4 czerwca
    Status:
    Published
    DOI:
    link to the publication

  21. Mutacja miejsca wiążącego (B2E155) w receptorze GABAA typu a1b2g2 wpływa na etap wiązania i bramkowania tego kanału

    Authors:
    Magdalena E. Jatczak, Magdalena Kisiel, Marta M. Czyżewska, Marek Brodzki, Jerzy W. Mozrzymas
    Conference:
    BioOpen I Ogólnopolska Konferencja Doktorantów Nauk o Życiu (year: 2015, pages: 188), Publisher: Uniwersytet Łódzki
    Date:
    conference 20-22 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  22. Receptory a1b2g2 i a1g2 receptora GABAA – porównanie właściwości farmakologicznych

    Authors:
    Radosław Rutkowski, Marek Brodzki, Marta M. Czyżewska, Magdalena Kisiel, Magdalena Jatczak, Jerzy W. Mozrzymas
    Conference:
    BioOpen I Ogólnopolska Konferencja Doktorantów Nauk o Życiu (year: 2015, pages: 196), Publisher: Uniwersytet Łódzki
    Date:
    conference 20-22 kwietnia
    Status:
    Published
    DOI:
    link to the publication

  23. Flurazepam enhances spontaneous activity of α1β2γ2L GABAA receptors, both wild-type and mutated at the α1F64 residue in the agonist binding

    Authors:
    Terejko K., Jatczak M, Brodzki M., Nowicka J., Andrzejczak A., Srinivasan R., Mozrzymas J.W.
    Conference:
    Aspects of Neuroscience (year: 2017, pages: 123-124), Publisher: Uniwersytet Warszawski
    Date:
    conference 24-26.11
    Status:
    Published

  24. Role of singly-bound states, spontaneous activity and the impact of α1F64 mutation at the agonist binding site of GABAA receptors revealed through kinetic modeling based on single-channel recordings

    Authors:
    Brodzki M., Jatczak M., Kisiel M., Mozrzymas J. W.
    Conference:
    7th Conference Aspects of Neuroscience (year: 2017, pages: 129-130), Publisher: Wydział Biologii Uniwersytetu Warszawskiego
    Date:
    conference 24-26.11.2017
    Status:
    Published

  25. Flurazepam modulates gating of spontaneous and agonist-evoked GABAA receptor activity via distinct mechanisms

    Authors:
    Jatczak-Śliwa M, Terejko K, Brodzki M, Michałowski MA, Czyzewska MM, Nowicka JM, Andrzejczak A, Rakenduvadhana S, Mozrzymas JW
    Conference:
    11th Conference on electrophysiological techniques in bioelectricity research (year: 2018, pages: 8, 9), Publisher: Acta Neurobiologiae Experimentalis
    Date:
    conference 25 - 26.05
    Status:
    Published

  26. Robust impact of flurazepam on spontaneous activity of GABAA receptors indicates modulation of gating transitions by benzodiazepines

    Authors:
    Brodzki M, Jatczak-Śliwa M., Terejko K., Michałowski M., Nowicka J., Andrzejczak A., Srinivasan R., Mozrzymas J.W.
    Conference:
    11th FENS Forum of Neuroscience (year: 2018, pages: 596), Publisher: Kenes Group
    Date:
    conference 07-11.07
    Status:
    Published
    DOI:
    link to the publication

  27. CHARACTERIZATION OF PHARMACOLOGICAL AND KINETIC PROFILES OF RECOMBINANT α1γ2 AND α1β2γ2 GABAA RECEPTORS

    Authors:
    Brodzki M, Rutkowski R, Jatczak M, Kisiel M, Czyżewska MM, Mozrzymas JW
    Conference:
    10th Conference on Electrophysiological Techniques in Bioelectricity Research: from Ion Channels to Neural Networks (year: 2016, pages: 3), Publisher: www.neuro.iz.uj.edu.pl
    Date:
    conference 03 - 04 czerwca
    Status:
    Published
    DOI:
    link to the publication

  28. Novel kinetic model of GABAAR activity based on single-channel recordings reveals the role of spontaneous gating, singly bound states and the impact of α1F64 mutation at the orthosteric binding site

    Authors:
    Brodzki M, Kisiel M, Jatczak M, Mozrzymas JW
    Conference:
    FENS Regional Meeting 2017 (year: 2017, pages: 74), Publisher: FENS Regional Meeting 2017
    Date:
    conference 20-23.09.2017
    Status:
    Published

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Graphic design and implementation: Jakub Piotrowski