Iris A Speigel1, Kishan Patel1, Hugh C Hemmings2. 1. Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA. 2. Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA. Electronic address: ias2006@med.cornell.edu.
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.
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.
Authors: Adekunle T Bademosi; James Steeves; Shanker Karunanithi; Oressia H Zalucki; Rachel S Gormal; Shu Liu; Elsa Lauwers; Patrik Verstreken; Victor Anggono; Frederic A Meunier; Bruno van Swinderen Journal: Cell Rep Date: 2018-01-09 Impact factor: 9.423
Authors: Jessica A Cardin; Marie Carlén; Konstantinos Meletis; Ulf Knoblich; Feng Zhang; Karl Deisseroth; Li-Huei Tsai; Christopher I Moore Journal: Nature Date: 2009-04-26 Impact factor: 49.962
Authors: Farhan Ali; Danielle M Gerhard; Katherine Sweasy; Santosh Pothula; Christopher Pittenger; Ronald S Duman; Alex C Kwan Journal: Nat Commun Date: 2020-01-07 Impact factor: 14.919