Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat supraoptic nucleus: role of N- and P/Q-type calcium channels
Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat supraoptic nucleus: role of N- and P/Q-type calcium channels
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DOI：
10.1111/j.1469-7793.2001.0595e.x
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发表时间：
2001-05-01
影响因子：
5.5
通讯作者：
Pittman, QJ
中科院分区：
文献类型：
--
作者：
Hirasawa, M;Kombian, SB;Pittman, QJ
1.我们以前报道过，催产素（OXT），从视上核（SON）的大细胞神经元的树突释放，逆行作用于突触前末梢，以抑制突触能传递。在这里，我们测试的假设，催产素减少钙流入突触前：终端。2.我们使用制霉菌素穿孔贴片记录在体外，首先确定在SON中的钙离子通道参与多巴胺能传输。ω-芋螺毒素GVIA（ω-CTx）和ω-Agatoxin TK（ω-阿加）均降低诱发的EPSC振幅，而尼卡地平和镍则无影响。ω-CTx和ω-阿加的组合完全消除了诱发的EPSC。这种电刺激效应伴随着成对脉冲比的增加，而诱发的EPSC、AMPA电流或突触后细胞特性的动力学没有变化。这些结果表明，突触前N型和P/Q型钙通道介导SON谷氨酸的释放，而L型、T型和R型钙通道几乎不起作用.催产素诱导的诱发EPSC的减少在ω-CTx的存在下基本上被闭塞，但在ω-Ag.5的存在下仅部分被闭塞。内肽酶抑制剂Amastatin可增加内源性OXT水平，也可降低诱发的EPSC。这种amastatin效应也被omega-CTx和omega-Aga阻断。不依赖于细胞外钙的微型EPSC不受ω-CTx或OXT的影响，因此进一步证实了两种化合物对钙通道的作用。因此，树突释放的催产素主要通过涉及N型通道的机制起作用，并且在较小程度上通过P/Q型通道起作用，以减少兴奋性传递。
1. We previously reported that oxytocin (OXT), released from the dendrites of magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on presynaptic terminals to inhibit glutamatergic transmission. Here we test the hypothesis that oxytocin reduces calcium influx into the presynaptic: terminal.2. We used nystatin perforated-patch recording in vitro to first identify the calcium channels involved in glutamatergic transmission in the SON. omega -Conotoxin GVIA (omega -CTx) and omega -Agatoxin TK (omega -Aga) both reduced evoked EPSC amplitude, while nicardipine and nickel had no effect. A combination of omega -CTx and omega -Aga completely abolished the evoked EPSCs.3. This depressant effect was accompanied by an increase in the paired pulse ratio with no change in the kinetics of the evoked EPSCs, AMPA currents or postsynaptic cell properties. These results suggest that presynaptic N- and P/Q-type calcium channels mediate glutamate release in the SON while L-, T- and R-type channels make little or no contribution.4. Oxytocin-induced reduction of the evoked EPSC was substantially occluded in the presence of omega -CTx but only partially in the presence of omega -Aga.5. Amastatin, an endopeptidase inhibitor that increases the level of endogenous OXT, also reduced the evoked EPSC. This amastatin effect was also occluded by omega -CTx and omega -Aga.6. Miniature EPSCs, which are independent of extracellular calcium, were unaffected by either omega -CTx or by OXT, thus further substantiating an action of both compounds on calcium channels.7. Therefore, dendritically released oxytocin acts mainly via a mechanism involving the N-type channel, and to a lesser extent the P/Q-type channel, to decrease excitatory transmission.