Lavoie Nathalie, Peralta Modesto R, Chiasson Marilou, Lafortune Kathleen, Pellegrini Luca, Seress László, Tóth Katalin
Centre de Recherche Université Laval Robert Giffard, 2601 chemin de la Canardière, Québec, Canada G1J 2G3.
J Physiol. 2007 Jan 1;578(Pt 1):275-89. doi: 10.1113/jphysiol.2006.121848. Epub 2006 Nov 9.
In the nervous system, zinc can influence synaptic responses and at extreme concentrations contributes to epileptic and ischaemic neuronal injury. Zinc can originate from synaptic vesicles, the extracellular space and from intracellular stores. In this study, we aimed to determine which of these zinc pools is responsible for the increased hippocampal excitability observed in zinc-depleted animals or following zinc chelation. Also, we investigated the source of intracellularly accumulating zinc in vulnerable neurons. Our data show that membrane-permeable and membrane-impermeable zinc chelators had little or no effect on seizure activity in the CA3 region. Furthermore, extracellular zinc chelation could not prevent the accumulation of lethal concentrations of zinc in dying neurons following epileptic seizures. At the electron microscopic level, zinc staining significantly increased at the presynaptic membrane of mossy fibre terminals in kainic acid-treated animals. These data indicate that intracellular but not extracellular zinc chelators could influence neuronal excitability and seizure-induced zinc accumulation observed in the cytosol of vulnerable neurons.
在神经系统中，锌可影响突触反应，在极高浓度时会导致癫痫和缺血性神经元损伤。锌可来源于突触小泡、细胞外空间和细胞内储存库。在本研究中，我们旨在确定这些锌库中哪一个是导致锌缺乏动物或锌螯合后海马兴奋性增加的原因。此外，我们还研究了易损神经元中细胞内锌积累的来源。我们的数据表明，膜通透性和膜非通透性锌螯合剂对CA3区的癫痫活动几乎没有影响。此外，细胞外锌螯合不能阻止癫痫发作后死亡神经元中致死浓度锌的积累。在电子显微镜水平上，在 kainic 酸处理的动物中，苔藓纤维终末的突触前膜上锌染色显著增加。这些数据表明，细胞内而非细胞外锌螯合剂可影响在易损神经元胞质中观察到的神经元兴奋性和癫痫诱导的锌积累。
