Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Jeong, Ji Ae; Kim, Eun Jin; Jo, Ji Yoon; Song, Jae Gyuk; Lee, Kyu Seung; Kim, Hyun Woo; Lee, Sang Do; Jeon, Byeong Hwa; Lee, Jung Un; Park, Jin Bong

doi:10.1016/j.neulet.2011.02.072

Cited by 6 publications

(8 citation statements)

References 37 publications

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“…Given all of these previous results, the amplified gamma response we observe here seems most likely to be caused by the potentiation of GABA A activity by propofol. Gamma amplitude changes could result from the enhancement of either phasic or tonic GABA currents, as propofol amplifies both [63], [64], [65] and both can modify gamma activity [62], [66]. The fact that both gamma amplitude and alpha suppression were enhanced suggests an overall increase in excitatory oscillatory effects with propofol.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

et al. 2013

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Stimulus-induced gamma oscillations in the 30–80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

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Section: Discussionmentioning

confidence: 99%

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

et al. 2013

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“…Despite the decrease in 24WD I tonic , similar characteristics of sIPSC in EU and 24WD rats suggested the selective postsynaptic alteration of GABA A R mediating I tonic in 24WD SON MNCs. To confirm this result, we tested and compared the effects of propofol on I phasic and I tonic in EU and 24WD rats; the general anaesthetic, propofol, potentiates I tonic but inhibits sIPSC frequency and delays IPSC decay time in SON MNCs .…”

Section: Resultsmentioning

confidence: 91%

“…The holding current (I holding ) and root mean square (RMS) noise were measured in 50‐ms epochs of traces lacking postsynaptic currents, separated by approximately 800 ms. Changes in RMS noise have been proposed to reflect changes in I tonic and have been used because they are unaffected by current drift. I tonic was defined as the difference in I holding before and after application of the GABA A receptor blocker BIC .…”

Section: Methodsmentioning

confidence: 99%

“…More than 45% of all synapses in the SON and PVN are immunoreactive for GABA , indicating a significant role of GABA in the nuclei. In SON MNCs, I tonic mediating the dominant portion of charge flows through GABA A Rs restrains spontaneous firing , and plays a substantial role in regulating neuronal excitability by endogenous neurosteroids and clinically important anaesthetics . However, the functional role of I tonic during physiological and pathophysiological challenges in SON MNCs is unknown.…”

mentioning

confidence: 99%

“…I tonic is generated mainly by benzodiazepine (BDZ)‐sensitive GABA A Rs containing the α 5 subunits in SON MNCs and, to a lesser extent, by the δ subunit‐containing receptors . In native GABA A Rs, δ and γ 2 subunits appear to be mutually exclusive and are responsible for the absence or presence of BDZ sensitivity, respectively .…”

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Attenuated Benzodiazepine‐Sensitive Tonic GABA_A Currents of Supraoptic Magnocellular Neuroendocrine Cells in 24‐h Water‐Deprived Rats

Pandit

Song

Kim

et al. 2014

J Neuroendocrinology

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In supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs), γ-GABA, via activation of GABAA receptors (GABAA Rs), mediates persistent tonic inhibitory currents (Itonic ), as well as conventional inhibitory postsynaptic currents (IPSCs, Iphasic ). In the present study, we examined the functional significance of Itonic in SON MNCs challenged by 24-h water deprivation (24WD). Although the main characteristics of spontaneous IPSCs were similar in 24WD compared to euhydrated (EU) rats, Itonic , measured by bicuculline (BIC)-induced Iholding shifts, was significantly smaller in 24WD compared to EU rats (P < 0.05). Propofol and diazepam prolonged IPSC decay time to a similar extent in both groups but induced less Itonic in 24WD compared to EU rats, suggesting a selective decrease in GABAA receptors mediating Itonic over Iphasic in 24WD rats. THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential δ subunit agonist, and L-655,708, a GABAA receptor α5 subunit selective imidazobenzodiazepine, caused a significantly smaller inward and outward shift in Iholding , respectively, in 24WD compared to EU rats (P < 0.05 in both cases), suggesting an overall decrease in the α5 subunit-containing GABAA Rs and the δ subunit-containing receptors mediating Itonic in 24WD animals. Consistent with a decrease in 24WD Itonic , bath application of GABA induced significantly less inhibition of the neuronal firing activity in 24WD compared to EU SON MNCs (P < 0.05). Taken together, the results of the present study indicate a selective decrease in GABAA Rs functions mediating Itonic as opposed to those mediating Iphasic in SON MNCs, demonstrating the functional significance of Itonic with respect to increasing neuronal excitability and hormone secretion in 24WD rats.

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The Pharmacology of Extrasynaptic GABAA Receptors

Wafford

2014

Extrasynaptic GABAA Receptors

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Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Cited by 6 publications

References 37 publications

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Attenuated Benzodiazepine‐Sensitive Tonic GABA_A Currents of Supraoptic Magnocellular Neuroendocrine Cells in 24‐h Water‐Deprived Rats

The Pharmacology of Extrasynaptic GABAA Receptors

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Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Cited by 6 publications

References 37 publications

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

Attenuated Benzodiazepine‐Sensitive Tonic GABAA Currents of Supraoptic Magnocellular Neuroendocrine Cells in 24‐h Water‐Deprived Rats

The Pharmacology of Extrasynaptic GABAA Receptors

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Attenuated Benzodiazepine‐Sensitive Tonic GABA_A Currents of Supraoptic Magnocellular Neuroendocrine Cells in 24‐h Water‐Deprived Rats