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Distinct effects of volatile and intravenous anaesthetics on presynaptic calcium dynamics in mouse hippocampal GABAergic neurones.

TitleDistinct effects of volatile and intravenous anaesthetics on presynaptic calcium dynamics in mouse hippocampal GABAergic neurones.
Publication TypeJournal Article
Year of Publication2022
AuthorsSpeigel IA, Patel K, Hemmings HC
JournalBr J Anaesth
Date Published2022 Feb 11
ISSN1471-6771
Abstract

BACKGROUND: General anaesthetics have marked effects on synaptic transmission, but their neuronal and circuit-level effects remain unclear. The volatile anaesthetic isoflurane differentially inhibits synaptic vesicle exocytosis in specific neuronal subtypes, but whether other common anaesthetics also have neurone-subtype-specific actions is unknown.

METHODS: We used the genetically encoded fluorescent Ca2+ sensor GCaMP6f to compare the pharmacological effects of isoflurane, sevoflurane, propofol, and ketamine on presynaptic excitability in hippocampal glutamatergic neurones and in hippocampal parvalbumin-, somatostatin-, and vasoactive intestinal peptide-expressing (PV+, SST+, and VIP+, respectively) GABAergic interneurones.

RESULTS: Isoflurane and sevoflurane depressed activity-driven presynaptic Ca2+ transients in a neurone-type-specific manner, with greater potency for inhibition of glutamate and SST+ compared with PV+ and VIP+ neurone presynaptic activation. In contrast, clinical concentrations of propofol (1 μM) or ketamine (15 μM) had no significant effects on presynaptic activation. Propofol potentiated evoked Ca2+ entry in PV+ interneurones but only at a supraclinical concentration (3 μM).

CONCLUSIONS: Anaesthetic-agent-selective effects on presynaptic Ca2+ entry have functional implications for hippocampal circuit function during i.v. or volatile anaesthetic-mediated anaesthesia. Hippocampal interneurones have distinct subtype-specific sensitivities to volatile anaesthetic actions on presynaptic Ca2+, which are similar between isoflurane and sevoflurane.

DOI10.1016/j.bja.2022.01.014
Alternate JournalBr J Anaesth
PubMed ID35164969