ArticleProceedings of the National Academy of Sciences of the United States of America2015
Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 100 citations in OpenAlex.
- Effects of Anesthesia Neurotoxicity on Oligodendrocyte Development and Myelination: An In Vitro Study Using Primary Cultures.International journal of molecular sciences · 2026Article
- Volatile anaesthetics modulate voltage-gated sodium channel function at a site directly linked to channel gating.Nature communications · 2026Article
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- Association between pyramidal neurone spiking in the medial prefrontal cortex and the sedative potency of volatile anaesthetics in mice.British journal of anaesthesia · 2025Article
- Astrocyte morphological remodeling regulates consciousness state transitions induced by inhaled general anesthesia.Molecular psychiatry · 2025Article
- Sevoflurane inhibition of the developmentally expressed neuronal sodium channel NaScientific reports · 2025Article
- Insight into molecular and neural mechanisms of general anesthesia from the invertebrate modelZoological research · 2025Review
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- An endogenous cholinergic system controls electrical conduction in the heart.European heart journal · 2025Article
- Assessment of changes in synaptic density in the zQ175DN mouse model of Huntington's disease: a [NeuroImage. Clinical · 2025Article
- The impact of ketamine and thiopental anesthesia on ultraweak photon emission and oxidative-nitrosative stress in rat brains.Frontiers in systems neuroscience · 2025Article
- Synapse-Specific Trapping of SNARE Machinery Proteins in the AnesthetizedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Mesoscopic mapping of hemodynamic responses and neuronal activity during pharmacologically induced interictal spikes in awake and anesthetized mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Article
- Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.Anesthesiology · 2024Article
- Noise-induced ribbon synapse loss in the mouse basal cochlear region does not reduce inner hair cell exocytosis.Frontiers in cellular neuroscience · 2024Article
- Volatile anesthetics inhibit presynaptic cGMP signaling to depress presynaptic excitability in rat hippocampal neurons.Neuropharmacology · 2023Article
- Article
- The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Neural Ensemble Fragmentation in the AnesthetizedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca(2+)]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca(2+) ([Ca(2+)]e). Lowering external Ca(2+) to match the isoflurane-induced reduction in Ca(2+) entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca(2+) entry without significant direct effects on Ca(2+)-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca(2+) influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.