Shaker-related potassium channels in the central medial nucleus of the thalamus are important molecular targets for arousal suppression by volatile general anesthetics
Open accessAbstract
The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family ( Shaker -related) delayed rectifier K + channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specific as microinfusion of ShK, a potent inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane-anesthetized rodents. In heterologous expression systems, sevoflurane, isoflurane, and desflurane at subsurgical concentrations potentiated delayed rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain slices, sevoflurane inhibited firing frequency and delayed the onset of action potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented these effects. Our findings demonstrate the exquisite sensitivity of delayed rectifier Kv1 channels to modulation by volatile anesthetics and highlight an arousal suppressing role of Kv1 channels in CMT neurons during the process of anesthesia.
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Localized infusion of KV1 channel inhibitors into the central thalamus of rodents reverses ongoing sevoflurane or desflurane anesthesia at steady-state, suggesting these channels help set arousal thresholds across evolutionarily distant species.
“Localized infusion of KV1 channel inhibitors into the central thalamus of rodents reverses ongoing sevoflurane or desflurane anesthesia at steady-state [59, 60], arguing that these channels play an important role in establishing arousal thresholds across evolutionarily distant species.”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [60]
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- Authors
- Lioudyno, M. I., Birch, A. M., Tanaka, B. S., Sokolov, Y., Goldin, A. L., Chandy, K. G., Hall, J. E., & Alkire, M. T.
- Affiliations
- University of California, Irvine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-10-09
- Volume
- 33
- Issue
- 41
- Pages
- 16310-16322
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3792466
- OpenAlex
- W2034859106
- Cited by
- 68
- References
- 71
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 10 · 2017: 9 · 2016: 6 · 2015: 6 · 2014: 1
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Larry L. Hillblom Foundation
- National Institutes of Health
- National Institute on Aging (P01AG032131)
- National Institute of Neurological Disorders and Stroke (R01NS048336, R01NS048252, NS048336)
- 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 › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- Kv1 potassium channels, Shaker channel, sevoflurane, isoflurane, desflurane, delayed rectifier potassium channel, Kv1.3 potassium channel, thalamic neurons
- MeSH terms
- Sevoflurane, Desflurane, Action Potentials, Animals, Arousal, Isoflurane, Male, Methyl Ethers, Mice, Inbred C57BL, Magnetic Resonance Spectroscopy, Rats, Sprague-Dawley, Patch-Clamp Techniques, Anesthetics, General, Intralaminar Thalamic Nuclei, Mice, Rats, Shaker Superfamily of Potassium Channels, Volatile Organic Compounds
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