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

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.

Keywords: calcium; interneurone; isoflurane; ketamine; mechanisms of anaesthesia; presynaptic; propofol; sevoflurane.