Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8516790 | Neuropharmacology | 2018 | 34 Pages |
Abstract
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 anesthetics interact with many ion channels and as some of them have neuroprotective effects, we hypothesized that inhalational anesthetics modulate ASICs. We expressed different homo- and heteromeric ASICs heterologously in Xenopus oocytes. We co-applied with acidic pH the halogenated inhalational anesthetics sevoflurane, desflurane, and isoflurane and the noble gases xenon and argon at concentrations that are roughly equivalent to their minimal alveolar concentrations and analyzed their effect on current kinetics and amplitude. Sevoflurane, desflurane, and isoflurane as well as xenon and argon accelerated by a factor of â¼1.5 channel desensitization of the main ASICs of the central nervous system: homomeric ASIC1a and heteromeric ASIC1a/2a and ASIC1a/2b. Moreover, they decreased current amplitudes by â¼25%. For example, isoflurane accelerated desensitization of homomeric ASIC1a from 1.0â¯Â±â¯0.4â¯s (meanâ¯Â±â¯SD) to 0.6â¯Â±â¯0.2â¯s (nâ¯=â¯12; pâ¯=â¯0.0003) and decreased current amplitudes from 12.1â¯Â±â¯7.5â¯Î¼A to 9.3â¯Â±â¯5.6â¯Î¼A (nâ¯=â¯12; pâ¯=â¯0.0009). While inhalational anesthetics had similar effects on homomeric ASIC3, desensitization of ASIC1b was only accelerated by halogenated anesthetics but not noble gases; desensitization of homomeric ASIC2a was not modulated. In summary, we found a significant modulation of ASICs by different inhalational anesthetics. We conclude that ASICs should be considered as relevant targets of inhalation anesthetics.
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Authors
Linda Lehmke, Mark Coburn, Manfred Möller, Rosmarie Blaumeiser-Debarry, Pia Lenzig, Dominik Wiemuth, Stefan Gründer,