The cellular and molecular actions of general anaesthetics to induce anaesthesia state and also cellular signalling changes for subsequent potential “long term” effects remain largely elusive although great efforts have been made to study these in vitro, ex vivo and in vivo settings. General anaesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on human embryonic primary prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted “microgliosis” but only sevoflurane changed microglia cell similarity. Propofol and sevoflurane each extensively but transiently altered transcriptome profiling 2 hours after anaesthetics exposure across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Within the excitatory neurons and microglia, exemplary ion-gated and ligand-gated ion channels related genes response to either anaesthetic included SCN1A, CACNAB2, KCNA1, GABRR2 and GRINA1 amongst many others. Utilising scRNA-seq as a robust and high-throughput tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anaesthetics in clinically relevant settings.

ARID5A, IER2, FOS, MICU2, JAKMIP1, RBM4B, ATP6V1D, HIF1AL, CNR1, NAV, PCLO, SLC25A39, IER3IP1, RTN4RL, HIF1A, CNR1, HIF-1α, ARID5A, IER2, FOS
CNR1, PI3K-Akt, ECM-receptor interaction, AMPK, TNF, CNR1, NAV2