Characterization of the participation of sodium channels on the rise in Na+ induced by 4-aminopyridine (4-AP) in synaptosomes
Characterization of the participation of sodium channels on the rise in Na+ induced by 4-aminopyridine (4-AP) in synaptosomes
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DOI：
10.1023/b:nere.0000013737.17288.ce
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Sitges, M
中科院分区：
文献类型：
--
作者：
Galván, E;Sitges, M
在纹状体突触体上研究了电压敏感性Na+通道（VSSC）对不同浓度4-AP引起的突触体内Na+、K+、Ca ~（2+）和DA、Glu、GABA释放变化的参与。TTX可消除0.1 mM 4-AP诱导的Na-1升高（用SBFI测定），但仅抑制1 mM 4-AP诱导的Na-1升高30%。1毫摩尔4-AP显著降低K+指示剂染料PBFI的荧光，但0.1 mM 4-AP没有。与ImM 4-AP一样，哇巴因以TTX不敏感的方式降低PBFI荧光并增加相当大比例的Na-1。与0.1和1 mM 4-AP引起的Na-i升高的不同TTX敏感性相比，TTX以及ω-芋螺毒素与ω-芋螺毒素GVIA的组合显著抑制了两种浓度的4-AP诱导的（用Fura-2测定），表明只有4-AP诱导的Na+升高的TTX敏感部分与突触前Ca 2+通道的激活有关。结论：4-AP诱发的神经递质释放的TTX敏感部分通过胞吐释放，而TTX不敏感部分涉及神经递质转运体的逆转。这与由TTX不变的高K+引起的胞吐作用和由藜芦碱引起的神经递质转运蛋白介导的释放形成对比，藜芦碱对TTX高度敏感，不需要激活Ca 2+通道。
The participation of voltage-sensitive Na+ channels (VSSC) on the changes on internal (i) Na+, K+, Ca2+, and on DA, Glu, and GABA release caused by different concentrations of 4-AP was investigated in striatum synaptosomes. TTX, which abolished the increase in Na-i (as determined with SBFI), induced by 0.1 mM 4-AP only inhibited by 30% the rise in Na-i induced by 1 mM 4-AP. One millimolar 4-AP markedly decreased the fluorescence of the K+ indicator dye PBFI but 0.1 mM 4-AP did not. Like 1 mM 4-AP, ouabain decreased PBFI fluorescence and increased a considerable fraction of Na-i in a TTX-insensitive manner. In contrast with the different TTX sensitivity of the rise in Na-i induced by 0.1 and 1 mM 4-AP, the rise in Ca-i (as determined with fura-2) induced by the two concentrations of 4-AP was markedly inhibited by TTX, as well as by omega-agatoxin in combination with omega-conotoxin GVIA, indicating that only the TTX-sensitive fraction of the rise in Na-i induced by 4-AP is linked with the activation of presynaptic Ca2+ channels. It is concluded that the TTX-sensitive fraction of neurotransmitter release evoked by 4-AP is released by exocytosis, and the TTX insensitive fraction involves reversal of the neurotransmitters transporters. This contrasts with the exocytosis evoked by high K+ that is unchanged by TTX and with the neurotransmitter-transporter-mediated release evoked by veratridine, which is highly TTX sensitive and does not require activation of Ca2+ channels.