G-Protein-Coupled Modulation of Presynaptic Calcium Currents and Transmitter Release by a GABAB Receptor

G-Protein-Coupled Modulation of Presynaptic Calcium Currents and Transmitter Release by a GABAB Receptor
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GABAB 受体对突触前钙电流的 G 蛋白耦合调节和递质释放

DOI:
10.1523/jneurosci.18-09-03138.1998
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发表时间:
1998
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
T. Tsujimoto
T. Tsujimoto
中科院分区:
--
文献类型:
--
作者:
Tomoyuki Takahashi;Y. Kajikawa;T. Tsujimoto

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突触前GABAB受体在中枢突触传递中起调节作用。为了阐明其潜在的作用机制,我们在大鼠脑干切片的梯形体内侧核中对巨大的突触前终末Held花萼和突触后靶点EPSCs的钙和钾电流进行了全细胞记录。GABAB受体激动剂巴氯芬抑制EPSCs和突触前钙电流,但对电压依赖性钾电流无影响。巴氯芬应用期间测量的钙电流- epsc关系与还原[Ca2+]o时观察到的相似,表明巴氯芬产生的突触前抑制主要是由抑制突触前钙内流引起的。突触前加载GDP类似物鸟苷-5′- o -(2-硫代二磷酸)(GDPβ s)消除了巴氯芬对突触前钙电流和EPSCs的影响。不可水解的GTP类似物鸟苷5′- o -(3-硫代三磷酸)(GTPγ s)抑制突触前钙电流,并阻断巴氯芬对突触前钙电流和EPSCs的影响。gtp - γ - s的光激活在花萼处诱导向内整流钾电流,而巴氯芬则没有这种作用。我们得出结论,突触前GABAB受体通过g蛋白偶联抑制钙电流来抑制递质释放。
Presynaptic GABAB receptors play a regulatory role in central synaptic transmission. To elucidate their underlying mechanism of action, we have made whole-cell recordings of calcium and potassium currents from a giant presynaptic terminal, the calyx of Held, and EPSCs from its postsynaptic target in the medial nucleus of the trapezoid body of rat brainstem slices. The GABAB receptor agonist baclofen suppressed EPSCs and presynaptic calcium currents but had no effect on voltage-dependent potassium currents. The calcium current–EPSC relationship measured during baclofen application was similar to that observed on reducing [Ca2+]o, suggesting that the presynaptic inhibition generated by baclofen is caused largely by the suppression of presynaptic calcium influx. Presynaptic loading of the GDP analog guanosine-5′-O-(2-thiodiphosphate) (GDPβS) abolished the effect of baclofen on both presynaptic calcium currents and EPSCs. The nonhydrolyzable GTP analog guanosine 5′-O-(3-thiotriphosphate) (GTPγS) suppressed presynaptic calcium currents and occluded the effect of baclofen on presynaptic calcium currents and EPSCs. Photoactivation of GTPγS induced an inward rectifying potassium current at the calyx of Held, whereas baclofen had no such effect. We conclude that presynaptic GABAB receptors suppress transmitter release through G-protein-coupled inhibition of calcium currents.
大鼠海马 CA3 区四氢氨基吖啶对突触后和突触前 GABAB 受体介导的反应的区分。
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