GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx
GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx
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DOI：
10.1016/j.ceca.2008.03.006
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发表时间：
2008-12-01
期刊：
影响因子：
4
通讯作者：
Edwards, Frances A.
中科院分区：
文献类型：
--
作者：
Donato, Roberta;Rodrigues, Ricardo J.;Edwards, Frances A.
在许多脑区，通过突触前P2 X受体的Ca 2+内流影响GABA从中间神经元的释放。用膜片钳技术记录大鼠小脑浦肯野细胞（PC），广谱P2受体拮抗剂PPADS（30 μ M）或苏拉明（12 μ M）可使篮状细胞诱发的GABA能突触电流的振幅降低，失败率增加。通过用α，β-亚甲基ATP使含有P2 X1/3的受体脱敏来模拟该效应。这表明突触前促进GABA释放通过P2 XR介导的Ca 2+内流激活内源性释放ATP。相反，P2 Y 4受体的激活（使用UTP，30 μ M，但不使用P2 Y1或P2 Y 6受体配体）导致GABA释放的抑制。免疫学研究揭示了大多数已知的P2 R存在于小脑中>= 20%的GABA能终末中。P2 X3受体和P2 Y 4受体分别存在于大约60%和50%的GABA能突触体中，并定位于突触前。以往的研究表明，PC的输出也受到位于PC和中间神经元上的突触后嘌呤能受体的影响，P2 X受体的高Ca ~（2+）通透性和ATP通过P2 Y受体介导的细胞内途径影响细胞内Ca ~（2+）水平的能力使ATP成为小脑皮质神经元网络多位点双向调节的理想递质。(c)2008年由Elsevier Ltd.出版
In many brain regions, Ca2+ influx through presynaptic P2X receptors influences GABA release from interneurones. In patch-clamp recordings of Purkinje cells (PCs) in rat cerebellar slices, broad spectrum P2 receptor antagonists, PPADS (30 mu M) or suramin (12 mu M), result in a decreased amplitude and increased failure rate of minimal evoked GABAergic synaptic currents from basket cells. The effect is mimicked by desensitizing P2X1/3-containing receptors with alpha,beta-methylene ATP. This suggests presynaptic facilitation of GABA release via P2XR-mediated Ca2+ influx activated by endogenously released ATP. In contrast, activation of P2Y4 receptors (using UTP, 30 mu M, but not P2Y1 or P2Y6 receptor ligands) results in inhibition of GABA release. Immunological studies reveal the presence of most known P2Rs in >= 20% of GABAergic terminals in the cerebellum. P2X3 receptors and P2Y4 receptors occur in approximately 60% and 50% of GABAergic synaptosomes respectively and are localized presynaptically. Previous studies report that PC output is also influenced by postsynaptic purinergic receptors located on both PCs and interneurones.The high Ca2+ permeability of the P2X receptor and the ability of ATP to influence intracellular Ca2+ levels via P2Y receptor-mediated intracellular pathways make ATP the ideal transmitter for the multisite bidirectional modulation of the cerebellar cortical neuronal network. (c) 2008 Published by Elsevier Ltd.