Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.
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DOI：
10.1371/journal.pone.0055673
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Valenzuela CF
中科院分区：
文献类型：
--
作者：
Diaz MR;Wadleigh A;Kumar S;De Schutter E;Valenzuela CF
小脑颗粒细胞（CGN）是表达时相性和紧张性GABA能传导的许多神经元之一。虽然已经确定高尔基体细胞（GoC）介导CGN中的相性GABA能电流，但是它们在介导CGN中的强直电流（CGN-Itonic）中的作用是有争议的。早期的研究表明，GoCs介导CGN-离子的一种组分，该组分仅存在于未成熟啮齿动物的制剂中。然而，最近的研究已经在成熟啮齿动物的制剂中检测到CGN-伊托尼的GoC依赖性组分。此外，急性暴露于乙醇被证明可以增强CGN-Itonic的GoC组分，并诱导CGN处自发抑制性突触后电流频率的平行增加。在这里，我们测试的假设，这些影响的乙醇对GABA能的传输CGN介导的抑制Na+/K+-ATP酶。我们使用全细胞膜片钳电生理技术在雄性大鼠小脑切片（出生后23-30天）。在这些条件下，我们可靠地检测到CGN-伊托宁的GoC依赖性组分，其可以被河豚毒素阻断。进一步的分析揭示了基础sIPSC频率和CGN-离子的GoC依赖性组分的幅度之间的正相关性。次最大浓度的哇巴因抑制Na+/K+-ATP酶部分模拟了乙醇诱导的CGN中的相性和紧张性GABA能电流的增强作用。建模研究表明，选择性抑制的Na+/K+-ATP酶在葡萄糖皮质激素，可以部分解释这些影响的乙醇。这些发现建立了乙醇对中枢神经系统中GABA能传递的新作用机制。
Cerebellar granule cells (CGNs) are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs) mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-Itonic) is controversial. Earlier studies suggested that GoCs mediate a component of CGN-Itonic that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-Itonic in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-Itonic and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na+/K+-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23–30). Under these conditions, we reliably detected a GoC-dependent component of CGN-Itonic that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-Itonic. Inhibition of the Na+/K+-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na+/K+-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.
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影响因子：
16.2
作者：
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通讯作者：
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影响因子：
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作者：
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