Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms
Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms
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DOI：
10.1111/j.1399-6576.2009.02047.x
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发表时间：
2009-11-01
影响因子：
2.1
通讯作者：
Berg-Johnsen, J.
中科院分区：
文献类型：
--
作者：
Bains, R.;Moe, M. C.;Berg-Johnsen, J.
背景与目的线粒体膜电位是线粒体主要功能的驱动力。七氟烷使神经线粒体去极化。然而，关于麻醉剂对人类神经线粒体的影响的信息仍然有限。七氟醚和丙泊酚对心肌细胞内Ca ~（2+）浓度[Ca ~（2+）]（i）和线粒体膜电位的影响因此，在大鼠和人类突触体中比较了Δ Psi（m），方法用荧光探针Fura-2负载大鼠和人大脑皮层突触体，（[Ca 2 +]（i））和JC-1（Δ Psi（m）），然后暴露于七氟烷1和2最低肺泡浓度（MAC）以及丙泊酚30和100 μ M。结果七氟醚和丙泊酚以剂量依赖性方式降低大鼠突触体中的Δ Psi（m），并以等效剂量达到相同程度。复合物V的抑制增强了七氟醚2 MAC的去极化作用，但不是丙泊酚100 μ M。七氟醚和丙泊酚对[Ca 2 +]（i）均无显著影响。七氟醚和丙泊酚降低Δ Psi（m）在人类突触体在大鼠experiments.ConclusionsSevoflurane和丙泊酚在等效剂量的大鼠和人类神经末梢的线粒体在相同程度上相同的程度。异丙酚对Psi（m）的去极化作用比七氟烷更快。七氟烷对呼吸链的抑制足以引起ATP合成酶逆转，而丙泊酚的去极化作用似乎与抑制复合物I至V的呼吸链有关。
Background and objectivesThe mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca2+ concentration [Ca2+](i) and the mitochondrial membrane potential (delta Psi(m)) was therefore compared in rat and human synaptosomes, and the changes were related to interventions in the electron transport chain.MethodsSynaptosomes from rat and human cerebral cortex were loaded with the fluorescent probes fura-2 ([Ca2+](i)) and JC-1 (delta Psi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 mu M. The effect on the electron transport chain was investigated by blocking complex V.ResultsSevoflurane and propofol decreased delta Psi(m) in rat synaptosomes in a dose-dependent manner, and to the same extent by equipotent doses. Inhibition of complex V enhanced the depolarizing effect of sevoflurane 2 MAC, but not of propofol 100 mu M. Neither sevoflurane nor propofol affected [Ca2+](i) significantly. Sevoflurane and propofol decreased delta Psi(m) in human synaptosomes to the same extent as in the rat experiments.ConclusionsSevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Psi(m) was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.