ArticleAnesthesiology2020
Volatile Anesthetics Activate a Leak Sodium Conductance in Retrotrapezoid Nucleus Neurons to Maintain Breathing during Anesthesia in Mice.
Article in Anesthesiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Volatile anesthetic sedation in acute respiratory distress syndrome.Intensive care medicine · 2026Review
- Convergent Control of NREM Sleep and Anesthesia by Prefrontal Layer 5 Extratelencephalic Neurons.Research square · 2025Article
- Stress-induced reduction of sodium leak currents causes social deficits by impairing dorsal dentate gyrus-medial septum glutamatergic projection.Molecular psychiatry · 2025Article
- Volatile anaesthetics for ICU sedation: beyond hypnosis?Critical care (London, England) · 2024Article
- Systematized Serendipity: Fishing Expeditions for Anesthetic Drugs and Targets.Anesthesiology · 2024Review
- Volatile anesthetics for lung- and diaphragm-protective sedation.Critical care (London, England) · 2024Review
- Astrocytes Modulate a Specific Paraventricular Thalamus→Prefrontal Cortex Projection to Enhance Consciousness Recovery from Anesthesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.Neuroscience bulletin · 2024Article
- The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.Current neuropharmacology · 2024Review
- General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis.iScience · 2023Article
- Increased Respiratory Drive after Prolonged Isoflurane Sedation: A Retrospective Cohort Study.Journal of clinical medicine · 2022Article
- The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Putative Roles of Astrocytes in General Anesthesia.Current neuropharmacology · 2022Review
- Comparison of etomidate and propofol-mediated anesthesia induction followed by intubation and sevoflurane maintenance during ERCP in obese patients.American journal of translational research · 2021Article
- Elevated Expression and Activity of Sodium Leak Channel Contributes to Neuronal Sensitization of Inflammatory Pain in Rats.Frontiers in molecular neuroscience · 2021Article
- Sodium Leak Channel in the Nucleus Accumbens Modulates Ethanol-Induced Acute Stimulant Responses and Locomotor Sensitization in Mice: A Brief Research Report.Frontiers in neuroscience · 2021Article
- Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review.Frontiers in synaptic neuroscience · 2021Review
- Isoflurane inhibits a Kir4.1/5.1-like conductance in neonatal rat brainstem astrocytes and recombinant Kir4.1/5.1 channels in a heterologous expression system.Journal of neurophysiology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundVolatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output.
methodsThe contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity.
resultsIsoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel-mediated holding currents and conductance from -75.0 ± 12.9 to -130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel-mediated holding conductance.
conclusionsIsoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics. EDITOR’S PERSPECTIVE:
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