Department of Experimental Medicine, University of Genova, Genova, Italy.
J Neurochem. 2010 Aug;114(4):1074-84. doi: 10.1111/j.1471-4159.2010.06829.x. Epub 2010 May 26.
Energy deprivation during ischemia causes dysregulations of ions, particularly sodium, potassium and calcium. Under these conditions, release of neurotransmitters is often enhanced and can occur by multiple mechanisms. The aim of this work was to characterize the modes of exit of glycine and GABA from nerve endings exposed to stimuli known to reproduce some of the ionic changes typical of ischemic conditions. Their approach was chosen instead of application of ischemic conditions because the release evoked during ischemia is mechanistically too heterogeneous. Mouse hippocampus and spinal cord synaptosomes, pre-labeled with [(3)H]glycine or [(3)H]GABA, were exposed in superfusion to 50 mM KCl or to 10 microM veratridine. The evoked overflows differed greatly between the two transmitters and between the two regions examined. Significant portions of the K(+)- and the veratridine-evoked overflows occurred by classical exocytosis. Carrier-mediated release of GABA, but not of glycine, was evoked by high K(+); GABA and, less so, glycine were released through transporter reversal by veratridine. External calcium-dependent overflows were only in part sensitive to omega-conotoxins; significant portions occurred following reversal of the plasmalemmal Na(+)/Ca(2+) exchanger. Finally, a relevant contribution to the overall transmitter overflows came from cytosolic calcium originating through the mitochondrial Na(+)/Ca(2+) exchanger. To conclude, ionic dysregulations typical of ischemia cause neurotransmitter release by heterogeneous mechanisms that differ depending on the transmitters and the CNS regions examined.
在缺血期间能量缺失会导致离子（尤其是钠、钾和钙）紊乱。在这些条件下，神经递质的释放通常会增强，并且可以通过多种机制发生。这项工作的目的是描述在暴露于已知可再现一些与缺血条件相关的离子变化的刺激下，神经末梢中甘氨酸和 GABA 释放的方式。之所以选择这种方法而不是应用缺血条件，是因为在缺血期间诱发的释放在机制上过于异质。用 [(3)H]甘氨酸或 [(3)H]GABA 预先标记的小鼠海马和脊髓突触体在灌注中暴露于 50 mM KCl 或 10 microM 藜芦碱。两种递质和两种检查区域之间的诱发溢出差异很大。K(+)-和藜芦碱诱发的溢出的显著部分通过经典的胞吐作用发生。高 K(+)可诱发 GABA 的载体介导释放，但不引起甘氨酸的释放；藜芦碱可引起 GABA 和甘氨酸的释放，通过转运体逆转。外钙依赖性溢出仅部分敏感于ω-芋螺毒素；在质膜 Na(+)/Ca(2+)交换体逆转后，会发生明显的部分溢出。最后，来自线粒体 Na(+)/Ca(2+)交换体的细胞质钙的重要贡献对整体递质溢出。总之，缺血时的离子失调会通过不同的机制引起神经递质的释放，这些机制因递质和检查的中枢神经系统区域而异。
