Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons

Abstract General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom exper...

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Main Authors: Casey Adam, Celine Kayal, Ari Ercole, Sonia Contera, Hua Ye, Antoine Jerusalem
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Communications Physics
Online Access:https://doi.org/10.1038/s42005-023-01252-7
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author Casey Adam
Celine Kayal
Ari Ercole
Sonia Contera
Hua Ye
Antoine Jerusalem
author_facet Casey Adam
Celine Kayal
Ari Ercole
Sonia Contera
Hua Ye
Antoine Jerusalem
author_sort Casey Adam
collection DOAJ
description Abstract General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general.
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spelling doaj.art-9c9c93f95e334a149c9c22f1a370139a2023-07-16T11:19:09ZengNature PortfolioCommunications Physics2399-36502023-07-016111110.1038/s42005-023-01252-7Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neuronsCasey Adam0Celine Kayal1Ari Ercole2Sonia Contera3Hua Ye4Antoine Jerusalem5Department of Engineering Science, University of OxfordDepartment of Engineering Science, University of OxfordDivision of Anaesthesia, University of Cambridge, Addenbrooke’s HospitalDepartment of Physics, University of OxfordDepartment of Engineering Science, University of OxfordDepartment of Engineering Science, University of OxfordAbstract General anaesthetics are widely used for their analgesic, immobilising, and hypnotic effects. The mechanisms underlying these effects remain unclear, but likely arise from alterations to cell microstructure, and potentially mechanics. Here we investigate this hypothesis using a custom experimental setup combining calcium imaging and nanoindentation to quantify the firing activity and mechanical properties of dorsal root ganglion-derived neurons exposed to a clinical concentration of 1% isoflurane gas, a halogenated ether commonly used in general anaesthesia. We found that cell viscoelasticity and functional activity are simultaneously and dynamically altered by isoflurane at different stages of exposure. Particularly, cell firing count correlated linearly with the neuronal loss tangent, the ratio of mechanical energy dissipation and storage by the cell. Our results demonstrate that anaesthetics affect cells as a whole, reconciling seemingly contradictory theories of how anaesthetics operate, and highlight the importance of considering cell mechanics in neuronal functions, anaesthesia, and clinical neuroscience in general.https://doi.org/10.1038/s42005-023-01252-7
spellingShingle Casey Adam
Celine Kayal
Ari Ercole
Sonia Contera
Hua Ye
Antoine Jerusalem
Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
Communications Physics
title Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
title_full Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
title_fullStr Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
title_full_unstemmed Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
title_short Action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
title_sort action of the general anaesthetic isoflurane reveals coupling between viscoelasticity and electrophysiological activity in individual neurons
url https://doi.org/10.1038/s42005-023-01252-7
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