Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism.
Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism.
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DOI：
10.1111/j.1530-0277.2011.01658.x
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Valenzuela CF
中科院分区：
文献类型：
--
作者：
Botta P;Simões de Souza FM;Sangrey T;De Schutter E;Valenzuela CF
对啮齿动物的研究表明，急性乙醇暴露损害通过小脑皮质的信息流，部分是通过增加颗粒细胞的GABA能输入。实验表明，调节颗粒细胞活性的专门GABA能中间神经元（即高尔基体细胞，GoC）的兴奋性增加有助于这种效应。在GoCs中，乙醇增加自发动作电位放电频率，降低后超极化幅度，并使膜电位去极化。研究表明，这些作用可能是通过抑制Na+/K+ ATP酶介导的。本研究的目的是表征其他GoC电导在乙醇作用机制中的潜在作用。采用计算机模拟技术和膜片钳技术对大鼠小脑急性脑片进行电生理记录。计算机模拟表明，阈下Na+通道，超极化激活电流和几个K+电导的调制可以解释一些，但不是所有的行动，乙醇对GoCs。电生理学研究没有发现与这些电导的贡献相一致的证据。奎尼丁是几种类型通道（包括几种K+通道）的非选择性阻断剂，也可拮抗Na+/K+ ATP酶，降低乙醇对GoC放电的影响。这些发现进一步支持了乙醇通过调节Na+/K+ ATP酶增加GoC兴奋性的结论，并表明奎尼丁敏感的K+通道也可能在乙醇的作用机制中发挥作用。
Studies with rodents suggest that acute ethanol exposure impairs information flow through the cerebellar cortex, in part, by increasing GABAergic input to granule cells. Experiments suggest that an increase in the excitability of specialized GABAergic interneurons that regulate granule cell activity (i.e. Golgi cells, GoCs) contributes to this effect. In GoCs, ethanol increases spontaneous action potential firing frequency, decreased the afterhyperpolarization amplitude, and depolarized the membrane potential. Studies suggest that these effects could be mediated by inhibition of the Na+/K+ ATPase. The purpose of this study was to characterize the potential role of other GoC conductances in the mechanism of action of ethanol. Computer modeling techniques and patch-clamp electrophysiological recordings with acute slices from rat cerebella were used for these studies. Computer modeling suggested that modulation of subthreshold Na+ channels, hyperpolarization activated currents and several K+ conductances could explain some but not all actions of ethanol on GoCs. Electrophysiological studies did not find evidence consistent with a contribution of these conductances. Quinidine, a non-selective blocker of several types of channels (including several K+ channels) that also antagonizes the Na+/K+ ATPase, reduced the effect of ethanol on GoC firing. These findings lend further support to the conclusion that ethanol increases GoC excitability via modulation of the Na+/K+ ATPase, and suggest that a quinidine-sensitive K+ channel may also play a role in the mechanism of action of ethanol.
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影响因子：
5.5
作者：
Forti, Lia;Cesana, Elisabetta;D'Angelo, Egidio
通讯作者：
D'Angelo, Egidio
影响因子：
5.5
作者：
Dieudonné, S
通讯作者：
Dieudonné, S
DOI：
10.1111/j.1530-0277.1998.tb03644.x
发表时间：
1998-02-01
影响因子：
3.2
作者：
Brodie, MS;Appel, SB
通讯作者：
Appel, SB
DOI：
10.1124/jpet.108.138370
发表时间：
2008-07-01
影响因子：
3.5
作者：
Horishita, Takafumi;Harris, R. Adron
通讯作者：
Harris, R. Adron
影响因子：
5.5
作者：
Holtzman, Tahl;Rajapaksa, Thimali;Edgley, Steve A.
通讯作者：
Edgley, Steve A.