Actions of acetylcholinesterase in the guinea-pig cerebellar cortex in vitro
Actions of acetylcholinesterase in the guinea-pig cerebellar cortex in vitro
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豚鼠小脑皮质乙酰胆碱酯酶的体外作用
DOI：
10.1016/0306-4522(92)90245-w
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发表时间：
1992
期刊：
影响因子：
3.3
通讯作者：
H. Jahnsen
中科院分区：
文献类型：
--
作者：
M. Appleyard;H. Jahnsen
当小脑皮质的传入神经受到刺激时，乙酰胆碱酯酶以钙依赖性方式释放。由于胆碱能传递在小脑皮质中可能微不足道，因此酯酶本身可能充当递质或调节剂。因此，在浦肯野细胞体体或树突的细胞内记录过程中，在豚鼠小脑切片中研究了乙酰胆碱酯酶在小脑中的作用。向灌注培养基中添加乙酰胆碱酯酶（20 U/ml）不会改变浦肯野细胞的膜电位或输入电阻。因此，酯酶的作用与经典递质不同。细胞内电流注入产生的Na+尖峰阈值不受影响，但Ca2+尖峰阈值增加。这种增加被河豚毒素 (1 μM) 消除。此外，当通过用 Mn2+ 代替 Ca2+ (2mM) 来阻断 Ca2+ 电流时，在酯酶存在下观察到 Na+ 平台电位下降。因此，乙酰胆碱酯酶对 Ca2+ 尖峰的影响很可能是由于浦肯野细胞膜非失活 Na+ 电流的减少所致。当存在时，该电流有助于激活树突中的 Ca2+ 尖峰。乙酰胆碱酯酶还增强了浦肯野细胞对兴奋性氨基酸谷氨酸和天冬氨酸的反应，这些氨基酸被认为是小脑皮质中的递质。在酯酶存在下，反应变得更大更快。乙酰胆碱酯酶也增强了对攀爬纤维刺激的反应。这种突触反应的后期部分有所增加。酯酶对浦肯野细胞对兴奋性氨基酸和攀爬纤维刺激的反应的增强可能是通过干扰递质摄取来介导的，因为用 dl-2-氨基-4-膦酸丁酸 (0.5 mM) 和二氢红藻氨酸 (0.1 mM) 处理可防止这种增强。酯酶的任何作用都不是由于乙酰胆碱的水解造成的，因为用梭曼对酶催化位点的不可逆抑制并不能阻止这些作用。观察结果针对乙酰胆碱酯酶。丁酰胆碱酯酶（20-40 U/ml）没有表现出任何影响。得出的结论是，小脑皮质中的乙酰胆碱酯酶似乎通过两种不同的机制介导一种新型的调节。酯酶降低浦肯野细胞中 Ca2+ 尖峰生成的趋势。 Ca2+尖峰之后是后超极化，并且在没有后超极化的情况下，可以以更高的频率发射Na+尖峰。其次，兴奋性递质的作用得到增强，从而可以利用扩展的操作范围。
Acetylcholinesterase is released in a calcium-dependent manner when afferents of the cerebellar cortex are stimulated. Since cholinergic transmission is probably insignificant in the cerebellar cortex, the esterase itself might serve as a transmitter or modulator. Therefore, the effect of acetylcholinesterase in the cerebellum was investigated in slices of guinea-pig cerebella during intracellular recording from Purkinje cell somata or dendrites. Addition of acetylcholinesterase (20 U/ml) to the superfusion medium did not change the membrane potential or the input resistance of the Purkinje cells. Thus, esterase does not act like a classical transmitter. The threshold for Na+spikes generated by intracellular current injection was unaffected, but the threshold for Ca2+spikes was increased. This increase was abolished by tetrodotoxin (1 μM). Furthermore, when Ca2+currents were blocked by substituting Mn2+for Ca2+(2mM) a decrease in a Na+plateau potential was seen in the presence of esterase. The effect of acetylcholinesterase on Ca2+spikes is therefore most likely due to a reduction of the non-inactivating Na+current of the Purkinje cell membrane. When present this current contributes to activation of Ca2+spikes in dendrites. Acetylcholinesterase also enhanced the response of Purkinje cells to the excitatory amino acids glutamate and aspartate thought to be transmitters in the cerebellar cortex. The responses became larger and faster in the presence of esterase. Responses to climbing fibre stimulation were also enhanced by acetylcholinesterase. The late part of this synaptic response was increased. The potentiation by esterase of responses of Purkinje cells to excitatory amino acids and to climbing fibre stimulation may be mediated through interference with transmitter uptake, because it was prevented by treatment withdl-2-amino-4-phosphonobutyric acid (0.5 mM) and di-hydrokainate (0.1 mM). None of the effects of esterase was due to hydrolysis of acetylcholine because irreversible inhibition of the catalytic site of the enzyme with soman did not prevent the actions. The observations were specific for acetylcholinesterase. Butyrylcholinesterase (20–40 U/ml) showed none of the effects.It is concluded that acetylcholinesterase in the cerebellar cortex seems to mediate a novel type of modulation by two separate mechanisms. Esterase reduces the tendency towards Ca2+spike generation in Purkinje cells. Ca2+spikes are followed by afterhyperpolarizations and in their absence firing of Na+spikes at higher frequencies is possible. Secondly, there is an enhancement of the action of excitatory transmitters so that the extended operating range can be utilized.
影响因子：
5.5
作者：
CHAN, CY;HOUNSGAARD, J;NICHOLSON, C
通讯作者：
NICHOLSON, C
影响因子：
5.5
作者：
LLINAS, R;SUGIMORI, M
通讯作者：
SUGIMORI, M