A dynamic clamp protocol to artificially modify cell capacitance
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.
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Capacitance Clamp Demonstration in Rat Dentate Gyrus Granule CellsZenodo. doi:10.5281/zenodo.5552207.
Article and author information
Author details
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
- Ronald L Calabrese, Emory University, United States
Publication history
- Received: November 12, 2021
- Accepted: March 17, 2022
- 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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Further reading
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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).