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 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.