Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic inhibition.
Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic inhibition.
复制标题
异丙酚通过减少 GABA 能抑制来刺激腹外侧视前核中去甲肾上腺素抑制的神经元。
DOI：
10.1213/ane.0b013e318297366e
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发表时间：
2013-08
影响因子：
5.7
通讯作者：
Ye JH
中科院分区：
文献类型：
--
作者：
Liu YW;Zuo W;Ye JH
全身麻醉药镇静作用的细胞机制还不完全清楚。越来越多的证据表明，下丘脑腹外侧视前区（VLPO）起着至关重要的作用。VLPO包含两种主要类型的神经元，去甲肾上腺素抑制的GABA能投射神经元（NA（−）神经元）和去甲肾上腺素兴奋的中间神经元（NA（+）神经元），后者可能也是含有γ-氨基丁酸（GABA）的神经元。我们以前的工作表明，NA（-）神经元通常在NA（+）神经元的抑制控制下。以往的研究也表明，GABA能药物，包括异丙酚激活的GABA能投射神经元在VLPO，这被认为是导致的抑制，在结节乳头核和镇静的觉醒产生的核。然而，丙泊酚如何激活VLPO神经元仍不清楚。我们探讨了丙泊酚通过抑制GABA能传递（包括来自VLPO NA（+）神经元的GABA能传递）间接激活NA（-）神经元的可能性。在大鼠急性脑片上记录了VLPO细胞的电生理活动。异丙酚促进NA（-）神经元的放电，降低NA（-）神经元自发GABA能抑制性突触后电流的频率，但不降低其幅度。相反，异丙酚抑制NA（+）神经元的放电。丙泊酚通过减少GABA能传递，至少部分通过抑制VLPO NA（+）神经元，兴奋VLPO NA（-）神经元。这可能是丙泊酚诱导镇静的一个重要机制。
The cellular mechanisms underlying the sedative effect of general anesthetics are not completely understood. Accumulating evidence indicates that the ventrolateral preoptic area (VLPO) of the hypothalamus plays a critical role. The VLPO contains two major types of neurons, the noradrenalin-inhibited GABAergic projecting neurons (NA(−) neurons), and the noradrenalin-excited interneurons (NA(+) neurons) which are probably also gamma-aminobutyric acid (GABA)-containing neurons. Our previous work suggests that NA(−) neurons are normally under the inhibitory control of NA(+) neurons. Previous studies also show that GABAergic agents including propofol activate GABAergic projecting neurons in the VLPO, which is believed to lead to the inhibition of the arousal-producing nuclei in the tuberomammillary nucleus and sedation. However, how propofol activates VLPO neurons remains unclear. We explored the possibility that propofol activates NA(−) neurons indirectly, by inhibiting GABAergic transmission including those from VLPO NA(+) neurons. Electrophysiological activities were recorded from VLPO cells in acute brain slices of rats. Propofol facilitates the discharges of NA(−) neurons and reduces the frequency, but not the amplitude of spontaneous GABAergic inhibitory postsynaptic currents in NA(−) neurons. Conversely, propofol suppressed the discharges of NA(+) neurons. Propofol excites VLPO NA(−) neurons by reducing GABAergic transmission, at least in part by inhibiting VLPO NA(+) neurons. This may be a critical mechanism contributing to propofol-induced sedation.