Inhalational anesthetics accelerate desensitization of acid-sensing ion channels

Lehmke, Linda; Coburn, Mark; Möller, Manfred; Blaumeiser-Debarry, Rosmarie; Lenzig, Pia; Wiemuth, Dominik; Gründer, Stefan

doi:10.1016/j.neuropharm.2018.04.004

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…Acid sensing ion channels (ASIC) are sodium channels, insensitive to voltage but sensitive to pH changes, that might have a role in regulating neurotransmitter release. In xenopus oocytes transfected with various rat ASIC subtypes, One study reported that xenon reduced the decay time of currents induced by acidic environments for the three ASIC subtypes expressed in the CNS, as well as reducing current amplitude for the ASIC 1α homomeric subtype (Lehmke et al, 2018).…”

Section: Other Membrane Bound Proteinsmentioning

confidence: 99%

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

McGuigan,

Marie,

O'Bryan

et al. 2023

Front. Neurosci.

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IntroductionXenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection.MethodsA systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included both in vitro models of the central nervous system and mammalian in vivo studies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed.ResultsThe review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection.DiscussionThe nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: 336871.

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Section: Other Membrane Bound Proteinsmentioning

confidence: 99%

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

McGuigan,

Marie,

O'Bryan

et al. 2023

Front. Neurosci.

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“…Recently, a common mechanism of argon and xenon has been identified. Both noble gases desensitise acid-sensing ion channels which was shown to be neuroprotective in mouse models of ischaemic stroke 23 . Regarding the anaesthetic effect of argon under hyperbaric conditions, GABA A -receptors appear to be involved 24 .…”

Section: Introductionmentioning

confidence: 99%

Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation

Suleiman

Klassen

Katz

et al. 2019

Sci Rep

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Argon exerts neuroprotection. Thus, it might improve patients’ neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (Pcap) were measured and the precapillary and postcapillary resistance (Rpost) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of Pcap, Rpost and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naïve pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABAB-receptors abolished argon-induced relaxation (p < 0.05) in naïve or ET-1-pre-contracted PAs; whereas inhibition of GABAA-receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABAA/B-receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABAB-agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure.

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Fluorine-Containing Inhalation Anesthetics: Chemistry, Properties and Pharmacology

Wang

Ming

Zhang

2020

CMC

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: The stories of fluorinated inhalation anesthetics, including synthesis, physicochemistry and pharmacologies, were summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was resplaced by enflurane in the 1970s. Isoflurane took the place of enflurane in the 1980s, showing modest advantages (e.g., lower solubility, better metabolic stability, and without convulsive predisposition). Desflurane and sevoflurane came into use in the 1990s, which are better anesthetics than isoflurane (less hepatotoxicity, lower solubility, and/or markedly decreased pungency). However, they are still less than perfect. To gain more ideal inhalation anesthetics, a large number of fluorinated halocarbons, polyfluorocycloalkanes, polyfluorocycloalkenes, fluoroarenes, and polyfluorooxetanes, were prepared and their potency and toxicity were evaluated. Although the pharmacology studies suggested that some of these agents produced anesthesia, no further works were continued on these compounds because they showed obvious shortages as anasthetics. Moreover, the anesthetic activity cannot be simply predicted from the molecular structures, and it has to be inferred from the experiments. Several regularities were found by experimental studies: 1) the potency and toxicity of the saturated linear chain halogenated ether are enhanced when its molecular weight is increased; 2) the margin of safety decreases and the recovery time is prolonged when the boiling point of the candidate increases; and 3) compounds with an asymmetric carbon terminal exhibit good anesthesia. Nevertheless, the development of new inhalation anesthetics better than desflurane and sevoflurane is still challenging not only because of the poor structure/activity relationship known so far but also the synthetic issues.

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Inhalational anesthetics accelerate desensitization of acid-sensing ion channels

Cited by 3 publications

References 43 publications

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature

Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation

Fluorine-Containing Inhalation Anesthetics: Chemistry, Properties and Pharmacology

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