Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness

Yang, Jane; Shakil, Husain; Ratté, Stéphanie; Prescott, Steven A

doi:10.7554/elife.72875

Cited by 41Ion channel regulation and functionNeural dynamics and brain functionstochastic dynamics and bifurcation

Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness

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Yang, Jane, Shakil, Husain, Ratté, Stéphanie, Prescott, Steven A·2022·eLife

DOI 10.7554/elife.72875PMC PMC8986315

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Abstract

Neurons regulate their excitability by adjusting their ion channel levels. Degeneracy – achieving equivalent outcomes (excitability) using different solutions (channel combinations) – facilitates this regulation by enabling a disruptive change in one channel to be offset by compensatory changes in other channels. But neurons must coregulate many properties. Pleiotropy – the impact of one channel on more than one property – complicates regulation because a compensatory ion channel change that restores one property to its target value often disrupts other properties. How then does a neuron simultaneously regulate multiple properties? Here, we demonstrate that of the many channel combinations producing the target value for one property (the single-output solution set), few combinations produce the target value for other properties. Combinations producing the target value for two or more properties (the multioutput solution set) correspond to the intersection between single-output solution sets. Properties can be effectively coregulated only if the number of adjustable channels ( n in ) exceeds the number of regulated properties ( n out ). Ion channel correlations emerge during homeostatic regulation when the dimensionality of solution space ( n in − n out ) is low. Even if each property can be regulated to its target value when considered in isolation, regulation as a whole fails if single-output solution sets do not intersect. Our results also highlight that ion channels must be coadjusted with different ratios to regulate different properties, which suggests that each error signal drives modulatory changes independently, despite those changes ultimately affecting the same ion channels.

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Authors: Yang, J., Shakil, H., Ratté, S., & Prescott, S. A.
Affiliations: University of Toronto (CA)
Great Ormond Street Hospital (GB)
ORCID: Yang, Jane
Shakil, Husain
Ratté, Stéphanie
Prescott, Steven A
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2022-03-16
Volume: 11
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.72875
PMC: PMC8986315
OpenAlex: W4220827944
Cited by: 41
References: 90
Citations by year: 2026: 4 · 2025: 6 · 2024: 12 · 2023: 14 · 2022: 4 · 2021: 1
FWCI: 2.94
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: eLife (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Canadian Institutes of Health Research (Foundation Grant 167276)
Natural Sciences and Engineering Research Council of Canada (Discovery Grant RGPIN 436168)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
Keywords: neuronal excitability, ion channel modulation, degeneracy, pleiotropy, homeostatic regulation, solution space, error signal, robustness
MeSH terms: Homeostasis, Ion Channels, Neurons

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Minimal requirements for a neuron to coregulate many properties and the implications for ion channel correlations and robustness

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