Volatile anesthetics increase intracellular calcium in cerebrocortical and hippocampal neurons
Volatile anesthetics increase intracellular calcium in cerebrocortical and hippocampal neurons
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DOI：
10.1097/00000542-199904000-00029
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发表时间：
1999-04-01
期刊：
影响因子：
8.8
通讯作者：
Bickler, PE
中科院分区：
文献类型：
--
作者：
Kindler, CH;Eilers, H;Bickler, PE
背景资料：神经元细胞内钙离子浓度（[Ca 2 +]（i））的增加被认为是挥发性麻醉剂的重要作用，因为它们改变了影响神经传递的信号通路。然而，现有的数据麻醉诱导的增加[Ca 2 +]（i）confliction.Methods：在[Ca 2 +]的变化，在大鼠大脑皮层切片在90，185，370，和705 μ M异氟烷使用Fura-2荧光光谱测定。为了确定[Ca 2 +]（i）增加的原因，在无Ca 2+培养基中，在存在Ca 2+通道阻滞剂和存在Ca 2+释放抑制剂azumolene的情况下研究了切片。作者比较了挥发性麻醉剂与非麻醉剂化合物1，2-二氯六氟环丁烷的效果。加州的单剂量实验！结果：异氟醚在0.5 μ M、1 μ M和2 μ M的最小肺泡浓度下以剂量依赖性方式增加皮层脑片的基础[Ca ~（2+）]（i）（P < 0.05）。这种增加不改变钙通道阻滞剂或钙的介质，但减少了85% azumolene。非麻醉剂1，2-二氯六氟环丁烷不增加[Ca 2 +]（i）。异氟醚可逆性地增加分离的海马CA 1区神经元的基础[Ca 2 +]（i）15 nM（P < 0.05），氟烷可逆性地增加分离的海马CA 1区神经元和海马脑片神经元的[Ca 2 +]（i）50 nM（P < 0.05）。(2)[Ca 2 +]（i）的增加主要是由细胞内储存的释放引起的。(3)[Ca 2 +]（i）的增加发生在麻醉剂中，但不发生在非麻醉剂1，2-二氯六氟环丁烷中。
Background: An increase in intracellular calcium concentration ([Ca2+](i)) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+](i) conflict.Methods: Changes in [Ca2+], were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 mu M isoflurane. To define the causes of an increase in [Ca2+](i), slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+ release Inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA! neurons in hippocampal slices with halothane (360 mu M) and in acutely dissociated CAI neurons with halothane (360 mu M) and isoflurane (445 mu M) also were performed.Results: Isoflurane at 0.5, i, and 2 minimum alveolar concentrations increased basal [Ca2+](i) in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+](i). In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+](i) by 15 nM (P < 0.05), Halothane increased [Ca2+](i) in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately SO nM (P < 0.05).Conclusions: (1) Isoflurane and halothane reversibly increase [Ca2+](i) in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+](i) is caused primarily by release from intracellular stores. (3) Increases in [Ca2+](i) occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.