Cell-surface biotinylation of GABAA receptors in mouse hippocampal slices after sevoflurane anesthesia

Ariza, Anthony; Naeini, Setareh Malekian; Khodaei, Shahin; Ba, Joycelyn; Wang, Dian-Shi; Orser, Beverley A.

doi:10.1016/j.xpro.2023.102450

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…12,73,74 As an example, a surprising finding is that expression of α5GABA A Rs on the cell surface of neurons increases for days after a brief exposure to general anesthetic drugs such as isoflurane, sevoflurane, and etomidate. 10,75 Others have since shown that propofol and the benzodiazepine diazepam similarly increase α5GABA A Rs in the plasma membrane. 76 By increasing α5GABA A R activity, anesthetic drugs cause subtle memory deficits that persist for at least 24 h. 10 These results were unexpected because for years, I, like many other anesthesiologists, have administered anesthetic drugs to patients with the assumption that the brain rapidly returns to its baseline state after drug elimination.…”

Section: Properties Of Extrasynaptic Gaba a Receptors Your Data Caref...mentioning

confidence: 99%

Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors

Orser

2024

Anesthesiology

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Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by α5 subunit-containing γ-aminobutyric acid type A receptors. By Caraiscos VB, Elliott EM, You-Ten KE, Cheng VY, Belelli D, Newell JG, Jackson MF, Lambert JJ, Rosahl TW, Wafford KA, MacDonald JF, Orser BA. Proc Natl Acad Sci U S A 2004; 101:3662–7. Reprinted with permission. In this Classic Paper Revisited, the author recounts the scientific journey leading to a report published in the Proceedings of the National Academy of Sciences (PNAS) and shares several personal stories from her formative years and “research truths” that she has learned along the way. Briefly, the principal inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA), was conventionally thought to regulate cognitive processes by activating synaptic GABA type A (GABAA) receptors and generating transient inhibitory synaptic currents. However, the author’s laboratory team discovered a novel nonsynaptic form of tonic inhibition in hippocampal pyramidal neurons, mediated by extrasynaptic GABAA receptors that are pharmacologically distinct from synaptic GABAA receptors. This tonic current is highly sensitive to most general anesthetics, including sevoflurane and propofol, and likely contributes to the memory-blocking properties of these drugs. Before the publication in PNAS, the subunit composition of GABAA receptors that generate the tonic current was unknown. The team’s research showed that GABAA receptors containing the α5 subunit (α5GABAARs) generated the tonic inhibitory current in hippocampal neurons. α5GABAARs are highly sensitive to GABA, desensitize slowly, and are thus well suited for detecting low, persistent, ambient concentrations of GABA in the extracellular space. Interest in α5GABAARs has surged since the PNAS report, driven by their pivotal roles in cognitive processes and their potential as therapeutic targets for treating various neurologic disorders.

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Section: Properties Of Extrasynaptic Gaba a Receptors Your Data Caref...mentioning

confidence: 99%

Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors

Orser

2024

Anesthesiology

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Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs

Wang,

Ju,

Pinguelo

et al. 2024

Translational Research

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Cell-surface biotinylation of GABAA receptors in mouse hippocampal slices after sevoflurane anesthesia

Cited by 2 publications

References 16 publications

Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors

Discovering the Intriguing Properties of Extrasynaptic γ-Aminobutyric Acid Type A Receptors

Crosstalk between GABAA receptors in astrocytes and neurons triggered by general anesthetic drugs

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