Inhalational anaesthetics accelerate desensitisation of acid-sensing ion channels

Acid-sensing ion channels (ASICs) are neuronal Na+ channels that are activated by extracellular acidification. Inhibiting ASICs is neuroprotective in mouse models of ischemic stroke. As inhalational anaesthetics interact with many ion channels and as some of them have neuroprotective effects, the authors hypothesised that inhalational anaesthetics modulate ASICs. Different homo- and heteromeric ASICs heterologously in Xenopus oocytes were expressed. The authors co-applied with acidic pH the halogenated inhalational anaesthetics sevoflurane, desflurane, and isoflurane and the noble gases xenon and argon at concentrations that are roughly equivalent to their minimal alveolar concentrations and analysed their effect on current kinetics and amplitude. Sevoflurane, desflurane, and isoflurane as well as xenon and argon accelerated by a factor of ?1.5 channel desensitisation of the main ASICs of the central nervous system: homomeric ASIC1a and heteromeric ASIC1a/2a and ASIC1a/2b. Moreover, they decreased current amplitudes by ?25%. For example, isoflurane accelerated desensitization of homomeric ASIC1a from 1.0?±?0.4?s (mean?±?SD) to 0.6?±?0.2?s (n?=?12; p?=?0.0003) and decreased current amplitudes from 12.1?±?7.5??A to 9.3?±?5.6??A (n?=?12; p?=?0.0009). While inhalational anaesthetics had similar effects on homomeric ASIC3, desensitisation of ASIC1b was only accelerated by halogenated anaesthetics but not noble gases; desensitisation of homomeric ASIC2a was not modulated. The authors found a significant modulation of ASICs by different inhalational anaesthetics. It was concluded that ASICs should be considered as relevant targets of inhalation anaesthetics.

Authors: Lehmke L, Coburn M, Möller M, Blaumeiser-Debarry R, Lenzig P, Wiemuth D, Gründer S. ; Full Source: Neuropharmacology. 2018 Apr 5; 135:496-505. doi: 10.1016/j.neuropharm.2018.04.004. [Epub ahead of print]

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