Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties
| العنوان: | Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties |
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| المؤلفون: | Olaf S. Andersen, Karl F. Herold, R. Lea Sanford, William A. Lee, Margaret F Schultz, Helgi I. Ingólfsson, Hugh C. Hemmings |
| المصدر: | The Journal of General Physiology |
| بيانات النشر: | Rockefeller University Press, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Physiology, Sodium, Lipid Bilayers, chemistry.chemical_element, Voltage-Gated Sodium Channels, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sodium channel blocker, 030202 anesthesiology, Animals, Lipid bilayer, Research Articles, Ion channel, 030304 developmental biology, Neurons, Volatile Organic Compounds, 0303 health sciences, Dose-Response Relationship, Drug, Isoflurane, Chemistry, GABAA receptor, Sodium channel, 3. Good health, Fluorobenzenes, Electrophysiology, nervous system, Biochemistry, Anesthetics, Inhalation, Gramicidin, lipids (amino acids, peptides, and proteins), Ion Channel Gating, Sodium Channel Blockers |
| الوصف: | Volatile anesthetics act directly on neuronal sodium channels, independently of effects on the lipid bilayer. Although general anesthetics are clinically important and widely used, their molecular mechanisms of action remain poorly understood. Volatile anesthetics such as isoflurane (ISO) are thought to alter neuronal function by depressing excitatory and facilitating inhibitory neurotransmission through direct interactions with specific protein targets, including voltage-gated sodium channels (Nav). Many anesthetics alter lipid bilayer properties, suggesting that ion channel function might also be altered indirectly through effects on the lipid bilayer. We compared the effects of ISO and of a series of fluorobenzene (FB) model volatile anesthetics on Nav function and lipid bilayer properties. We examined the effects of these agents on Nav in neuronal cells using whole-cell electrophysiology, and on lipid bilayer properties using a gramicidin-based fluorescence assay, which is a functional assay for detecting changes in lipid bilayer properties sensed by a bilayer-spanning ion channel. At clinically relevant concentrations (defined by the minimum alveolar concentration), both the FBs and ISO produced prepulse-dependent inhibition of Nav and shifted the voltage dependence of inactivation toward more hyperpolarized potentials without affecting lipid bilayer properties, as sensed by gramicidin channels. Only at supra-anesthetic (toxic) concentrations did ISO alter lipid bilayer properties. These results suggest that clinically relevant concentrations of volatile anesthetics alter Nav function through direct interactions with the channel protein with little, if any, contribution from changes in bulk lipid bilayer properties. Our findings further suggest that changes in lipid bilayer properties are not involved in clinical anesthesia. |
| تدمد: | 1540-7748 0022-1295 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::443d3e803bb0d2b48e1d3458b164fdc1Test https://doi.org/10.1085/jgp.201411172Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....443d3e803bb0d2b48e1d3458b164fdc1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15407748 00221295 |
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