P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses.

P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses.
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P 型电压依赖性钙通道介导哺乳动物突触中的突触前钙流入和递质释放。

DOI:
10.1073/pnas.89.8.3330
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发表时间:
1992
影响因子:
11.1
通讯作者:
Llinás,R
Llinás,R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Uchitel,OD;Protti,DA;Sanchez,V;Cherksey,BD;Sugimori,M;Llinás,R

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我们研究了从漏斗网蜘蛛毒液(FTX)纯化的毒素及其合成类似物(sFTX)对小鼠神经肌肉连接处递质释放和突触前电流的影响。FTX特异性阻断小脑浦肯野细胞中omega- concontoxin -和二氢吡啶-不敏感的p型电压依赖性Ca2+通道(VDCC)。哺乳动物对N-或l型Ca2+通道阻滞剂不敏感的神经肌肉传递被FTX和sFTX有效地消除。这些物质阻断了神经刺激引起的肌肉收缩和神经递质释放。此外,从支配小鼠耳提肌的神经周围鞘内部记录的细胞外突触前Ca2+电流被天然毒素和合成类似物特异性阻断。在一组平行的实验中,脑突触体对K(+)诱导的Ca45摄取也被FTX和sFTX阻断或大大减少。这些结果表明,运动神经末梢的主要VDCC是p型通道,可能在很大比例的脑突触中也是如此。
We have studied the effect of the purified toxin from the funnel-web spider venom (FTX) and its synthetic analog (sFTX) on transmitter release and presynaptic currents at the mouse neuromuscular junction. FTX specifically blocks the omega-conotoxin- and dihydropyridine-insensitive P-type voltage-dependent Ca2+ channel (VDCC) in cerebellar Purkinje cells. Mammalian neuromuscular transmission, which is insensitive to N- or L-type Ca2+ channel blockers, was effectively abolished by FTX and sFTX. These substances blocked the muscle contraction and the neurotransmitter release evoked by nerve stimulation. Moreover, presynaptic Ca2+ currents recorded extracellularly from the interior of the perineural sheaths of nerves innervating the mouse levator auris muscle were specifically blocked by both natural toxin and synthetic analogue. In a parallel set of experiments, K(+)-induced Ca45 uptake by brain synaptosomes was also shown to be blocked or greatly diminished by FTX and sFTX. These results indicate that the predominant VDCC in the motor nerve terminals, and possibly in a significant percentage of brain synapses, is the P-type channel.