Propofol suppresses synaptic respon

Propofol suppresses synaptic responsiveness of somatosensory
relay neurons to excitatory input by potentiating GABAA receptor
chloride channels
Abstract
Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in
humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli.
However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely
unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical
relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both
current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal
summation and action potential firing were evoked in VB neurons by electrical stimulation of
corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 µM)
suppressed temporal summation and spike firing in a concentration-dependent manner. The
thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and
input resistance, indicating that a shunting mechanism was involved. The propofol-mediated
thalamocortical suppression could be blocked by a GABAA receptor antagonist or chloride channel
blocker, suggesting that postsynaptic GABAA receptors in VB neurons were involved in the
shunting inhibition. GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) were
evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly
increased amplitude, decay time, and charge transfer of GABAA IPSCs. The results demonstrated
that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant
concentrations is primarily mediated through the potentiation of the GABAA receptor chloride
channel-mediated conductance, and such inhibition may contribute to the impaired thalamic
responses to sensory stimuli seen during propofol-induced anesthesia.

結果 (繁體中文) 1:

丙泊酚抑制突觸反應的體感中繼神經元興奮性輸入由增效 GABAA 受體氯通道摘要丙泊酚是廣泛使用的靜脈全身麻醉。丙泊酚誘導無意識中人類是與抑制誘發體感刺激丘腦活動相關聯。然而，異丙酚在丘腦電路中的作用的細胞機制很大程度上是未知。我們研究了丙泊酚對丘腦-皮質突觸反應性的影響在腹側複雜 (VB) 對小鼠腦片，同時使用這二者的興奮性輸入中繼神經元電流和電壓-鉗記錄技術。興奮性反應包括 EPSP 時間求和與動作電位射擊了在 VB 神經元電刺激誘發的丘腦纖維或藥理谷氨酸受體的啟動。丙泊酚 (0.6-3 µ M)抑制時間總和和穗射擊呈濃度依賴性。的丘腦-皮質抑制陪同兩個 EPSP 振幅明顯減少和輸入的電阻，該值指示一個分流機制被涉及。介導丙泊酚丘腦-皮質抑制可以堵住 GABAA 受體拮抗劑或氯離子通道阻滯劑，暗示，VB 神經元突觸後的 GABAA 受體參與了調車的抑制作用。GABAA 受體介導的抑制突觸後電流 （誘導多能幹細胞） 了在 VB 神經元誘發電刺激丘腦網狀。丙泊酚明顯增加幅度、 衰減時間和電荷轉移的 GABAA 誘導多能幹細胞。結果表明那分流抑制丘腦的體感中繼神經元由丙泊酚在臨床相關主要介導通過長時程增強的 GABAA 受體氯的濃度通道介導的電導和這種抑制作用可能有助於受損丘腦對異丙酚麻醉期間看到的感官刺激的反應。

結果 (繁體中文) 2:

異丙酚體感抑制突觸反應
通過加強GABAA受體神經元繼電器興奮性輸入
氯離子通道
摘要
異丙酚是一種廣泛使用的靜脈全身麻醉。異丙酚誘導無意識中
人類與抑制體感誘發刺激丘腦的活動有關。
然而，潛在的異丙酚在丘腦電路的影響細胞機制在很大程度上是
未知的。我們研究了丘腦皮層突觸反應異丙酚的影響，
在腹側複雜（VB）在鼠腦切片興奮性輸入繼電器的神經元，同時使用
電流，電壓鉗記錄技術。包括EPSP時間興奮的反應
總結和動作電位發放VB中神經元的電刺激誘發了
corticothalamic纖維或谷氨酸受體的活化藥。丙泊酚（0.6 - 3μM）
抑制時間總和，穗射擊的濃度依賴性。在
丘腦皮層抑制伴隨著在兩個EPSP幅值和顯著減少
的輸入阻抗，這表明一個分流機制參與。異丙酚介導
丘腦皮層抑制可以由GABA A受體拮抗劑或氯通道被阻塞
阻滯劑，這表明在VB神經元突觸後GABAA受體參與了
分流抑制。GABAA受體介抑制性突觸後電流（IPSC的）都
在VB神經元丘腦網狀核的電刺激誘發。異丙酚明顯
增加幅度，衰減時間，和GABAA IPSC的電荷轉移。結果表明
，在臨床相關分流丘腦體感中繼神經元的抑制異丙酚
濃度是通過GABAA受體氯化物的增強作用主要是介導的
通道介導的電導，並且這種抑制可以向受損丘腦
到propofol-期間看到的感官刺激的反應誘導麻醉。