Ethanol decreases Purkinje neuron excitability by increasing GABA release in rat cerebellar slices.
Ethanol decreases Purkinje neuron excitability by increasing GABA release in rat cerebellar slices.
复制标题
乙醇通过增加大鼠小脑切片中 GABA 的释放来降低浦肯野神经元的兴奋性。
DOI：
10.1124/jpet.108.144865
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Valenzuela CF
中科院分区：
文献类型：
--
作者：
Mameli M;Botta P;Zamudio PA;Zucca S;Valenzuela CF
小脑浦肯野神经元（PN）接受抑制性GABA能输入的星状细胞和篮状细胞，这是位于外部和内部的分子层，分别。最近显示乙醇（EtOH）通过涉及从突触前内部储存增强的钙释放的机制增加PN处的GABA能传递（Kelm等人，药理学实验治疗学杂志323：356-64，2007）。在这里，我们进一步表征了乙醇对GABA释放的影响，并评估了其对PN兴奋性的影响。采用全细胞膜片钳电生理技术在小脑蚓旁脑片，我们发现，乙醇急性增加的频率，但不是幅度或半宽度的微型和自发的抑制性突触后电流（IPSC）。EtOH可显著增加IPSC的振幅，降低IPSC的成对脉冲比，但对内分子层无影响。在电流钳，乙醇降低幅度的EPSPs引起的颗粒细胞轴突刺激和这些事件触发的动作电位的数量，这些影响依赖于GABAA受体激活，因为它们没有观察到荷包牡丹碱的存在。松补丁细胞连接PN记录显示，无论是自发动作电位放电频率，也不是变异系数的峰间期被改变急性乙醇暴露。这些研究结果表明，EtOH对星状细胞和篮细胞至PN突触的GABA能传递有不同的影响，并且它调节颗粒细胞轴突输入触发的PN放电。这些影响可能是与急性乙醇中毒相关的小脑损伤的部分原因。
Cerebellar Purkinje neurons (PNs) receive inhibitory GABAergic input from stellate and basket cells, which are located in the outer and inner portions of the molecular layer, respectively. Ethanol (EtOH) was recently shown to increase GABAergic transmission at PNs via a mechanism that involves enhanced calcium release from presynaptic internal stores (Kelm et al., J Pharmacol Exp Ther. 323:356-64, 2007). Here, we further characterized the effect of EtOH on GABA release and assessed its impact on PN excitability. Using whole-cell patch-clamp electrophysiological techniques in cerebellar vermis parasagittal slices, we found that EtOH acutely increases the frequency but not the amplitude or half-width of miniature and spontaneous inhibitory postsynaptic currents (IPSCs). EtOH significantly increased the amplitude and decreased the paired-pulse ratio of IPSCs evoked by stimulation in the outer but not inner molecular layer. In current-clamp, EtOH decreased both the amplitude of EPSPs evoked in PNs by granule cell axon stimulation and the number of action potentials triggered by these events; these effects depended on GABAA receptor activation as they were not observed in presence of bicuculline. Loose-patch cell-attached PN recordings revealed that neither the spontaneous action potential firing frequency nor the coefficient of variation of the interspike interval were altered by acute EtOH exposure. These findings suggest that EtOH differentially affects GABAergic transmission at stellate cell- and basket cell-to-PN synapses and that it modulates PN firing triggered by granule cell axonal input. These effects could be in part responsible for the cerebellar impairments associated with acute EtOH intoxication.
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影响因子：
5.3
作者：
Ariwodola, OJ;Weiner, JL
通讯作者：
Weiner, JL
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2.5
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FREUND, RK;WANG, Y;PALMER, MR
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PALMER, MR
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LEE, RS;SMITH, SS;WOODWARD, DJ
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