Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration
Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration
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卡巴胆碱对体外海马神经元的影响：依赖于卡巴胆碱组织浓度的上升速率
DOI：
10.1007/bf00250251
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发表时间：
2004
影响因子：
2
通讯作者：
U. Heinemann
中科院分区：
文献类型：
--
作者：
W. Müller;U. Misgeld;U. Heinemann
本研究采用钾敏感微电极测定卡巴胆碱（carbachol，CCh）在豚鼠海马脑片上的浓度和作用时间依赖性。通过用500 μM胆碱预平衡切片并在存在相同胆碱浓度的情况下校准CCh敏感微电极来中和可能源自组织胆碱化合物的干扰。用细胞内记录法观察了CCh对颗粒细胞和CA 3区锥体神经元动作电位的毒蕈碱性去极化和后超极化（AHP）的减少。设计了一种CCh快速水浴施用模式，CCh组织浓度在2-3 min后达到峰值，约8 min的半衰期被冲洗掉，以这种方式施用30 nmol CCh后，根据CCh浓度随时间的变化降低AHP。神经元在AHP降低后有一定的延迟去极化，并在组织CCh浓度达到峰值（0.6 μM）前1 min开始恢复。哌仑西平（1-10 μM）仅阻断去极化，而阿托品（1-10 μM）既阻断去极化又阻断AHP的还原。当灌流含生理盐水的CCh，80%的最终浓度达到浴后12分钟，但在组织中只有45分钟后。组织CCh浓度的缓慢增加是同步的AHP的缓慢下降。未观察到对膜电位的影响。阿托品，但不是哌仑西平，阻止了AHP的减少。灌流高浓度的CCh（100-300 μM）可使神经元去极化，降低AHP。然后哌仑西平使神经元复极化，而阿托品使细胞复极化并恢复AHP。结果表明，毒蕈碱去极化不仅与CCh浓度有关，而且与CCh的上升速率有关，而AHP的降低仅与浓度有关。这一结果进行了讨论的可能性，即去极化介导的短期脱敏M1毒蕈碱受体亚型和减少的AHP介导的M2毒蕈碱受体亚型。
SummaryNominally K-sensitive microelectrodes were used to measure carbachol (CCh) in order to study the dependence of muscarinic effects on CCh concentration and exposure time in guinea pig hippocampal slices. Interference presumably originating from tissue choline-compounds was neutralized by pre-equilibration of the slices with 500 μM choline and calibration of the CCh-sensitive microelectrodes in the presence of the same choline-concentration. Muscarinic depolarization and reduction of the afterhyperpolarization (AHP) following a train of action potentials by bath applied CCh were monitored in granule cells and CA3 pyramidal neurons by intracellular recording. A fast bath application mode of CCh was designed, by which CCh tissue concentration reached a peak after 2–3 min and was washed out with a half time of about 8 min. After application of 30 nmol CCh in this way, the AHP was reduced according to the variation of CCh concentration over time. Neurons depolarized with some delay after the reduction of the AHP and started to repolarize 1 min before the peak of tissue CCh concentration (0.6 μM) was reached. Pirenzepine (1–10 μM) blocked only the depolarization, while atropine (1–10 μM) blocked both the depolarization and the reduction of the AHP. When superfusing with CCh containing saline, 80% of the final concentration was reached in the bath after 12 min, but in the tissue only after 45 min. The slow increase of tissue CCh concentration was concurrent with the slow decrease of the AHP. No effect on the membrane potential was observed. Atropine, but not pirenzepine, blocked the reduction of the AHP. Superfusion with a high CCh concentration (100–300 μM) containing saline depolarized neurons and reduced the AHP. Then pirenzepine repolarized neurons, whereas atropine both repolarized the cells and restored the AHP. It is concluded that the muscarinic depolarization depends not only on the CCh concentration, but also on the rate of rise of CCh, while the reduction of the AHP depends solely on the concentration. This result is discussed in terms of the possibility that the depolarization is mediated by a short term desensitizing M1 muscarinic receptor subtype and the reduction of the AHP is mediated by a M2 muscarinic receptor subtype.
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鼠神经母细胞瘤克隆 (N1E-115) 中的毒蕈碱反应和结合：环 GMP 形成由低亲和力激动剂-受体构象介导，环 AMP 还原由高亲和力激动剂-受体构象介导。
影响因子：
3.6
作者：
McKinney,M;Richelson,E
通讯作者：
Richelson,E
影响因子：
5.5
作者：
NICHOLSON, C;PHILLIPS, JM
通讯作者：
PHILLIPS, JM
培养的小鼠神经母细胞瘤细胞对毒蕈碱受体介导的环 GMP 合成的调节。
影响因子：
4.7
作者：
El-Fakahany,E;Richelson,E
通讯作者：
Richelson,E
鼠神经母细胞瘤克隆 (N1E-115) 中的毒蕈碱反应和结合。
影响因子：
3.6
作者：
McKinney,M;Stenstrom,S;Richelson,E
通讯作者：
Richelson,E