The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptors and P2x purinoceptors in PC12 cells.
The effects of ketamine and propofol on neuronal nicotinic acetylcholine receptors and P2x purinoceptors in PC12 cells.
复制标题
氯胺酮和丙泊酚对 PC12 细胞中神经元烟碱乙酰胆碱受体和 P2x 嘌呤受体的影响。
作者：
R. Furuya;K. Oka;I. Watanabe;Y. Kamiya;H. Itoh;T. Andoh
无标签
用全细胞电压钳记录技术研究了氯胺酮和异丙酚对大鼠嗜铬细胞瘤细胞株PC12神经元型烟碱型乙酰胆碱受体(NAChRs)和P2X嘌呤受体的作用。氯胺酮和异丙酚同样可逆地抑制尼古丁诱发的内向电流，并呈剂量依赖关系，膜电位为-60 mV，但对三磷酸腺苷诱导的电流无影响。两种麻醉剂都加速了激动剂应用过程中的电流衰减，导致对稳定电流的抑制比峰值电流更大。稳定电流的50%抑制浓度低于氯胺酮的临床相关浓度(2.8±0.6微米)，高于异丙酚的浓度(5.4±0.6微米)。两种麻醉剂均可使快成分增加到衰减期，而使慢成分加速，提示开放通道阻断或增强脱敏是其机制之一。对关闭的通道的影响似乎很小，因为与麻醉剂预先孵育并不能显著增强阻滞性。膜电位在-20~-70 mV范围内，抑制作用与电压无关，符合非竞争性阻断。抑制神经元nAchR介导的电流可能导致临床相关浓度的氯胺酮抑制交感神经节的突触传递，而异丙酚不能抑制交感神经节的突触传递。然而，这些结果与报道的用氯胺酮或异丙酚麻醉的动物或人类的交感神经活动变化不一致，这表明来自其他系统的影响，如体内的中枢神经系统。
影响
氯胺酮(小于临床相关浓度)和异丙酚(大于临床相关浓度)抑制PC12细胞烟碱型乙酰胆碱受体介导的电流，PC12细胞具有与节后交感神经元相似的受体。这些发现与体内实验不一致，这表明来自其他系统的影响，如中枢神经系统，是重要的。
UNLABELLED
We studied the effects of ketamine and propofol on two ligand-gated ion channels mediating fast synaptic transmission through sympathetic ganglia, neuronal nicotinic acetylcholine receptors (nAchRs), and P2X purinoceptors in a rat pheochromocytoma cell line PC12 using whole cell voltage clamp recording. Ketamine and propofol similarly inhibited the nicotine-induced inward current reversibly and dose-dependently at the membrane potential of -60 mV but had no effects on the adenosine triphosphate-induced current. Both anesthetics accelerated the current decay during agonist application, resulting in greater inhibition on the steady current than the peak current. The 50% inhibition concentration values for the steady current were lower than the clinically relevant concentrations for ketamine (2.8+/-0.6 microM) and higher than those for propofol (5.4+/-0.6 microM). Both anesthetics induced an addition of the fast component to the decay phase and an acceleration of the slow component, which suggests an open channel blockade or an enhancement of desensitization as a mechanism. The effects on closed channels seemed to be small because preincubation with the anesthetics did not significantly augment the block. Inhibition was voltage-independent at membrane potentials between -20 and -70 mV and was consistent with a noncompetitive block. Inhibition of the neuronal nAchR-mediated current may lead to the suppression of synaptic transmission in sympathetic ganglia by ketamine, but not by propofol, at the clinically relevant concentrations. However, these results are not consistent with changes in sympathetic nerve activities reported for animals or humans anesthetized with ketamine or propofol, which suggests effects from other systems, such as the central nervous system in vivo.
IMPLICATIONS
Ketamine (at smaller than clinically relevant concentrations) and propofol (at larger than clinically relevant concentrations) inhibited neuronal nicotinic acetylcholine receptor-mediated current in PC12 cells, which possess the receptors that resemble those in postganglionic sympathetic neurons. These findings are not consistent with in vivo experiments, which suggests that effects from other systems, such as the central nervous system, are of importance.
影响因子：
3.6
作者：
S. Forman;K. Miller;G. Yellen
通讯作者：
S. Forman;K. Miller;G. Yellen