Effects of anesthetics on ATP sensitive K channels in rat substantia nigra dopamine neurons.

麻醉剂对大鼠黑质多巴胺神经元 ATP 敏感 K 通道的影响。

• 批准号: 12671494
• 负责人: ANDOH Tomio
• 金额: $ 2.3万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671494/
• 关键词: isoflurane; ketamine; ATP sensitive K channel; Substantia Nigra; neuron; brain protection; インフルレン

While it is shown that some of general anesthetics have modulatory effects on ATP sensitive K channels (KATP) in cardiac myocytes and smooth muscle cells, their effects on neuronal KATP are poorly understood. We have investigated effects of two different anesthetics on neuronal ATP sensitive K channels (KATP) in rat dopamine neurons located in substantia nigra pars compacts, using a slice patch technique.We measured the membrane potential and current with the pipette solutions containing ATP either 2 mM, 1 mM or 0 mM. Daizoxide or intracellular ATP depletion by exclusion of ATP from the pipette solution hyperpolarized the neurons and abolished spontaneous action potential firings in a tolbutamide sensitive manner. Isoflurane, a volatile anesthetic, induced a slight depolarization in the presence of intracellular ATP but did not alter the membrane potential after ATP was depleted at 2.2 MAC equivalent Isoflurane at 1 MAC equivalent caused no significant effects in either conditions. Activation of protein kinase C did not influence the effects of isoflurane, unlike to a previous study on cardiac sarcolemmal KATP. Ketamine, an intravenous anesthetic, did not affect the| membrane potential in the presence of ATP 2 mM but partially antagonized hyperpolarization and the outward current caused by ATP depletion at 100 μM. or above.These results suggest that isoflurane has no significant effects on KATP but ketamine has a blocking action on activated KATP in these neurons.

虽然有研究表明，一些全身麻醉剂对心肌细胞和平滑肌细胞中的ATP敏感K通道（ATP sensitive K channels， KATP）具有调节作用，但它们对神经元KATP的影响尚不清楚。我们使用切片贴片技术研究了两种不同麻醉剂对大鼠黑质致密部多巴胺神经元ATP敏感K通道（KATP）的影响。我们用含有2毫米、1毫米或0毫米ATP的移液管溶液测量了膜电位和电流。通过从移液管溶液中排除ATP， Daizoxide或细胞内ATP耗尽使神经元超极化，并以甲磺丁酰胺敏感的方式消除自发动作电位放电。异氟醚是一种挥发性麻醉剂，在细胞内ATP存在的情况下会引起轻微的去极化，但在ATP在2.2 MAC当量时耗尽后不会改变膜电位。蛋白激酶C的激活不影响异氟醚的作用，这与先前对心肌细胞KATP的研究不同。静脉麻醉剂氯胺酮在ATP 2 mM存在时不影响|膜电位，但部分拮抗100 μM ATP耗竭引起的超极化和向外电流。或以上。这些结果表明异氟醚对KATP无显著影响，而氯胺酮对这些神经元中活化的KATP有阻断作用。