Alterations in oscillatory behavior of central medial thalamic neurons demonstrate a key role of CaV3.1 isoform of T-channels during isoflurane-induced anesthesia
Open accessAbstract
Although the central medial nucleus (CeM) of the thalamus is an essential part of the arousal system for sleep and anesthesia initiation, the precise mechanisms that regulate its activity are not well studied. We examined the role of CaV3.1 isoform of T-type calcium channels (T-channels) in the excitability and rhythmic activity of CeM neurons during isoflurane (ISO)-induced anesthesia by using mouse genetics and selective pharmacology. Patch-clamp recordings taken from acute brain slices revealed that CaV3.1 channels in CeM are inhibited by prototypical volatile anesthetic ISO (250 and 500 μM) and selective T-channels blocker 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2). Both TTA-P2 and ISO attenuated tonic and burst firing modes, and hyperpolarized CeM neurons from wild type (WT) mice. These effects were greatly diminished or abolished in CaV3.1 null mice. Our ensuing in vivo local field potential (LFP) recordings from CeM indicated that the ability of TTA-P2 and anesthetic concentrations of ISO to promote δ oscillation was substantially weakened in CaV3.1 null mice. Furthermore, escalating ISO concentrations induced stronger burst-suppression LFP pattern in mutant than in WT mice. Our results demonstrate for the first time the importance of CaV3.1 channels in thalamocortical oscillations from the non-specific thalamic nuclei that underlie clinically important effects of ISO.
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Volatile anesthetic modulation of CaV3.1 channels in midline thalamic nuclei alters thalamocortical rhythms in mice; under identical isoflurane, CaV3.1 knockout mice show decreased slow-wave EEG and increased burst suppression.
“Volatile anesthetic-induced modulation of CaV3.1 channel function in midline thalamic nuclei alters thalamocortical rhythms in mice. Under identical isoflurane exposures, compared to sibling controls, CaV3.1 knock-out mice exhibit decreased slow-wave EEG activity, which is often associated with hypnosis, and increased EEG burst suppression, which typifies states of deeper anesthesia [68].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [68]
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The Biology of General Anesthesia from Paramecium to Primate
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- Authors
- Timic Stamenic, T., Feseha, S., Valdez, R., Zhao, W., Klawitter, J., & Todorovic, S. M.
- Affiliations
- Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- University of Colorado Anschutz (US)
- Corresponding author
- Todorovic, Slobodan M
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-01-31
- Volume
- 29
- Issue
- 11
- Pages
- 4679-4696
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC6917523
- OpenAlex
- W2913413637
- Cited by
- 28
- References
- 82
- Citations by year
- 2025: 5 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 1
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01GM102525)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- isoflurane anesthesia, thalamocortical oscillations, delta oscillations, burst suppression, neuronal excitability, volatile anesthetics, thalamus
- MeSH terms
- Anesthesia, Animals, Female, Isoflurane, Male, Membrane Potentials, Mice, Inbred C57BL, Neurons, Mice, Knockout, Protein Isoforms, Intralaminar Thalamic Nuclei, Calcium Channels, T-Type
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