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HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice
It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol an...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849183/ https://www.ncbi.nlm.nih.gov/pubmed/29560119 http://dx.doi.org/10.18632/oncotarget.24408 |
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author | Gao, Jie Hu, Zhiqiang Shi, Liwei Li, Na Ouyang, Yeling Shu, Shaofang Yao, Shanglong Chen, Xiangdong |
author_facet | Gao, Jie Hu, Zhiqiang Shi, Liwei Li, Na Ouyang, Yeling Shu, Shaofang Yao, Shanglong Chen, Xiangdong |
author_sort | Gao, Jie |
collection | PubMed |
description | It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics. Here we showed the EC(50) for propofol- and ketamine-induced loss-of-righting reflex (LORR) was significantly lower for P35 than for P14 mice. Cerebrospinal fluid concentrations of propofol and ketamine were significantly higher in P14 mice than in P35 mice, with similar propofol- and ketamine-induced anesthesia at the LORR EC(50). Western blotting indicated that the expression of HCN channels in neocortex changed significantly from P14 to P35 mice. In addition, the amplitude of HCN currents in the neocortical layer 5 pyramidal neurons and the inhibition of propofol and ketamine on HCN currents dramatically increased with development. Logistic regression analysis indicated that the changes of HCN channels were correlated with the age-related differences of propofol- and ketamine-induced anesthesia. These data reveal that the change of HCN channels expression with postnatal development may contribute to sensitivity to the hypnotic actions of propofol and ketamine in mice. |
format | Online Article Text |
id | pubmed-5849183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58491832018-03-20 HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice Gao, Jie Hu, Zhiqiang Shi, Liwei Li, Na Ouyang, Yeling Shu, Shaofang Yao, Shanglong Chen, Xiangdong Oncotarget Research Paper It is widely accepted that the induction dose of anesthetics is higher in infants than in adults, although the relevant molecular mechanism remains elusive. We previously showed neuronal hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to hypnotic actions of propofol and ketamine. Interestingly, the expression of HCN channels in neocortex significantly changes during postnatal periods. Thus, we postulated that changes in HCN channels expression might contribute to sensitivity to intravenous anesthetics. Here we showed the EC(50) for propofol- and ketamine-induced loss-of-righting reflex (LORR) was significantly lower for P35 than for P14 mice. Cerebrospinal fluid concentrations of propofol and ketamine were significantly higher in P14 mice than in P35 mice, with similar propofol- and ketamine-induced anesthesia at the LORR EC(50). Western blotting indicated that the expression of HCN channels in neocortex changed significantly from P14 to P35 mice. In addition, the amplitude of HCN currents in the neocortical layer 5 pyramidal neurons and the inhibition of propofol and ketamine on HCN currents dramatically increased with development. Logistic regression analysis indicated that the changes of HCN channels were correlated with the age-related differences of propofol- and ketamine-induced anesthesia. These data reveal that the change of HCN channels expression with postnatal development may contribute to sensitivity to the hypnotic actions of propofol and ketamine in mice. Impact Journals LLC 2018-02-05 /pmc/articles/PMC5849183/ /pubmed/29560119 http://dx.doi.org/10.18632/oncotarget.24408 Text en Copyright: © 2018 Gao et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Gao, Jie Hu, Zhiqiang Shi, Liwei Li, Na Ouyang, Yeling Shu, Shaofang Yao, Shanglong Chen, Xiangdong HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title | HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title_full | HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title_fullStr | HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title_full_unstemmed | HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title_short | HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
title_sort | hcn channels contribute to the sensitivity of intravenous anesthetics in developmental mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849183/ https://www.ncbi.nlm.nih.gov/pubmed/29560119 http://dx.doi.org/10.18632/oncotarget.24408 |
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