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

First Author  Speigel IA Year  2022
Journal  Br J Anaesth Volume  128
Issue  6 Pages  1019-1028
PubMed ID  35164969 Mgi Jnum  J:359607
Mgi Id  MGI:7788556 Doi  10.1016/j.bja.2022.01.014
Citation  Speigel IA, et al. (2022) Distinct effects of volatile and intravenous anaesthetics on presynaptic calcium dynamics in mouse hippocampal GABAergic neurones. Br J Anaesth 128(6):1019-1028
abstractText  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 Ca(2+) 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 Ca(2+) 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 muM) or ketamine (15 muM) had no significant effects on presynaptic activation. Propofol potentiated evoked Ca(2+) entry in PV(+) interneurones but only at a supraclinical concentration (3 muM). CONCLUSIONS: Anaesthetic-agent-selective effects on presynaptic Ca(2+) 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 Ca(2+), which are similar between isoflurane and sevoflurane.
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