scholarly journals Mapping the contribution of β3-containing GABAA receptors to volatile and intravenous general anesthetic actions

2007 ◽  
Vol 7 (1) ◽  
Author(s):  
Anja Zeller ◽  
Margarete Arras ◽  
Rachel Jurd ◽  
Uwe Rudolph
2017 ◽  
Vol 126 (4) ◽  
pp. 666-677 ◽  
Author(s):  
Dian-Shi Wang ◽  
Antonello Penna ◽  
Beverley A. Orser

Abstract Background The “dissociative ” general anesthetic ketamine is a well-known N-methyl-d-aspartate receptor antagonist. However, whether ketamine, at clinically relevant concentrations, increases the activity of inhibitory γ-aminobutyric acid (GABA) receptor type A (GABAA) receptors in different brain regions remains controversial. Here, the authors studied the effects of ketamine on synaptic and extrasynaptic GABAA receptors in hippocampal neurons. Ketamine modulation of extrasynaptic GABAA receptors in cortical neurons was also examined. Methods Whole cell currents were recorded from cultured murine neurons. Current evoked by exogenous GABA, miniature inhibitory postsynaptic currents, and currents directly activated by ketamine were studied. Results Ketamine did not alter the amplitude, frequency, or kinetics of postsynaptic currents but increased a tonic inhibitory current generated by extrasynaptic GABAA receptors in hippocampal neurons. For example, ketamine (100 µM) increased the tonic current by 33.6 ± 6.5% (mean ± SEM; 95% CI, 18.2 to 48.9; n = 8, P < 0.001). Ketamine shifted the GABA concentration–response curve to the left, but only when GABAA receptors were activated by low concentrations of GABA (n = 6). The selective increase in tonic current was attributed to ketamine increasing the apparent potency of GABA at high-affinity extrasynaptic GABAA receptors. Ketamine also increased a tonic current in cortical neurons (n = 11). Ketamine directly gated the opening of GABAA receptors, but only at high concentrations that are unlikely to occur during clinical use. Conclusions Clinically relevant concentrations of ketamine increased the activity of high-affinity extrasynaptic GABAA receptors in the hippocampus and cortex, an effect that likely contributes to ketamine’s neurodepressive properties.


2020 ◽  
Vol 194 ◽  
pp. 112261 ◽  
Author(s):  
Abdelrahman R. Shalabi ◽  
Zhiyi Yu ◽  
Xiaojuan Zhou ◽  
Youssef Jounaidi ◽  
Hanwen Chen ◽  
...  

2010 ◽  
Vol 8 (1) ◽  
pp. 2-9 ◽  
Author(s):  
Paul Garcia ◽  
Scott Kolesky ◽  
Andrew Jenkins

2017 ◽  
Vol 31 (4) ◽  
pp. 531-538 ◽  
Author(s):  
Masaki Hayashiuchi ◽  
Tomoya Kitayama ◽  
Katsuya Morita ◽  
Yosuke Yamawaki ◽  
Kana Oue ◽  
...  

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