Selective inhibition of gamma aminobutyric acid release from mouse hippocampal interneurone subtypes by the volatile anaesthetic isoflurane
| Autor: | Iris A. Speigel, Hugh C. Hemmings |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Mice Transgenic Voltage-Gated Sodium Channels Neurotransmission Hippocampal formation Hippocampus Synaptic Transmission Synaptic vesicle Exocytosis gamma-Aminobutyric acid Mice Glutamatergic Neuroscience and Neuroanaesthesia medicine Animals gamma-Aminobutyric Acid Neurons Isoflurane business.industry Cell biology Synaptic vesicle exocytosis Anesthesiology and Pain Medicine nervous system Gene Knockdown Techniques Anesthetics Inhalation Female business medicine.drug |
| Zdroj: | Br J Anaesth |
| ISSN: | 0007-0912 |
| DOI: | 10.1016/j.bja.2021.06.042 |
| Popis: | Background The cellular and molecular mechanisms by which general anaesthesia occurs is poorly understood. Hippocampal interneurone subpopulations, which are critical regulators of cognitive function, have diverse neurophysiological and synaptic properties, but their responses to anaesthetics are unclear. Methods We used live-cell imaging of fluorescent biosensors expressed in mouse hippocampal neurones to delineate interneurone subtype-specific effects of isoflurane on synaptic vesicle exocytosis. The role of voltage-gated sodium channel (Nav) subtype expression in determining isoflurane sensitivity was probed by overexpression or knockdown of specific Nav subtypes in identified interneurones. Results Clinically relevant concentrations of isoflurane differentially inhibited synaptic vesicle exocytosis: to 83.1% (11.7%) of control in parvalbumin-expressing interneurones, and to 58.6% (13.3%) and 64.5% (8.5%) of control in somatostatin-expressing interneurones and glutamatergic neurones, respectively. The relative expression of Nav1.1 (associated with lower sensitivity) and Nav1.6 (associated with higher sensitivity) determined the sensitivity of exocytosis to isoflurane. Conclusions Isoflurane inhibits synaptic vesicle exocytosis from hippocampal glutamatergic neurones and GABAergic interneurones in a cell-type-specific manner depending on their expression of voltage-gated sodium channel subtypes. |
| Databáze: | OpenAIRE |
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