Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice-Reference-Cited by-同舟云学术

Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice

Published:2024-04-16 Issue:1 Volume:141 Page:56-74
ISSN:0003-3022
Container-title:Anesthesiology
language:en
Short-container-title:

Author:

Wu Yujie¹^ORCID,Zhang Donghang²,Liu Jin³,Jiang Jingyao⁴,Xie Keyu⁵,Wu Lin⁶,Leng Yu⁷,Liang Peng⁸,Zhu Tao⁹,Zhou Cheng¹⁰^ORCID

Affiliation:

1. 1Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

2. 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

3. 3Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

4. 4Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

5. 5Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

6. 6Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

7. 7Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

8. 8Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

9. 9Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

10. 10Laboratory of Anesthesia and Critical Care Medicine, National–Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. Methods Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. Results Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. Conclusions Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Publisher

Ovid Technologies (Wolters Kluwer Health)

Link

https://pubs.asahq.org/anesthesiology/article-pdf/141/1/56/709300/20240700.0-00016.pdf

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