A dynamic clamp protocol to artificially modify cell capacitance

  1. Paul Pfeiffer
  2. Federico José Barreda Tomás
  3. Jiameng Wu
  4. Jan-Hendrik Schleimer
  5. Imre Vida
  6. Susanne Schreiber  Is a corresponding author
  1. Humboldt-Universität zu Berlin, Germany
  2. Charité - Universitätsmedizin Berlin, Germany

Abstract

Dynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances of excitable membranes are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows electrophysiologists to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique. We first demonstrate the feasibility to quantitatively modulate capacitance in a mathematical neuron model and then confirm the functionality of capacitance clamp in in vitro experiments in granule cells of rodent dentate gyrus with up to threefold virtual capacitance changes. Clamping of capacitance thus constitutes a novel technique to probe and decipher mechanisms of neuronal signaling in ways that were so far inaccessible to experimental electrophysiology.

Data availability

All data generated, analysis code as well as computational modelling code is uploaded on https://zenodo.org/, see article section Data and software availability.

The following data sets were generated

Article and author information

Author details

  1. Paul Pfeiffer

    Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5324-5886
  2. Federico José Barreda Tomás

    Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jiameng Wu

    Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Jan-Hendrik Schleimer

    Institute of Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Imre Vida

    Institute for Integrative Neuroanatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3214-2233
  6. Susanne Schreiber

    Institute of Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany
    For correspondence
    s.schreiber@hu-berlin.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3913-5650

Funding

Bundesministerium für Bildung und Forschung (01GQ1403)

  • Paul Pfeiffer
  • Jan-Hendrik Schleimer
  • Susanne Schreiber

Deutsche Forschungsgemeinschaft (GRK 1589/2)

  • Paul Pfeiffer
  • Federico José Barreda Tomás

Deutsche Forschungsgemeinschaft (EXC 257)

  • Federico José Barreda Tomás
  • Imre Vida

Deutsche Forschungsgemeinschaft (FOR 2134)

  • Federico José Barreda Tomás
  • Imre Vida

H2020 European Research Council (864243)

  • Paul Pfeiffer
  • Jan-Hendrik Schleimer
  • Susanne Schreiber

Einstein Stiftung Berlin (EZ-2014-224)

  • Jiameng Wu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures and animal maintenance were performaed in accordance with institutional guidelines, the German Animal Welfare Act, the European Council Directive 86/609/EEC regarding the protection of animals, and guidelines from local authorities (Berlin, T-0215/11).

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: November 12, 2021
  2. Accepted: March 17, 2022
  3. Accepted Manuscript published: April 1, 2022 (version 1)

Copyright

© 2022, Pfeiffer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Paul Pfeiffer
  2. Federico José Barreda Tomás
  3. Jiameng Wu
  4. Jan-Hendrik Schleimer
  5. Imre Vida
  6. Susanne Schreiber
(2022)
A dynamic clamp protocol to artificially modify cell capacitance
eLife 11:e75517.
https://doi.org/10.7554/eLife.75517

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    Funding: financial support for this work from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (GIG), an Ontario Graduate Scholarship (SS), a Restracomp Research Fellowship provided by the Hospital for Sick Children (SS), an Institutional Research Chair in Neuroinformatics (MD), as well as a Natural Sciences and Engineering Research Council CREATE grant (MD).