Osmolarity, ionic flux, and changes in brain excitability
Osmolarity, ionic flux, and changes in brain excitability
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DOI：
10.1016/s0920-1211(98)00058-8
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发表时间：
1998-09-01
影响因子：
2.2
通讯作者：
Hochman, DW
中科院分区：
文献类型：
--
作者：
Schwartzkroin, PA;Baraban, SC;Hochman, DW
大多数现代癫痫研究都集中在突触和内在神经元特性的可能异常，以及可能的致痫机制以及开发新型抗癫痫治疗的靶点。然而，中枢神经系统中的许多其他过程有助于神经元的兴奋性和同步性。离子平衡的调节就是这样一组关键过程，它涉及一系列复杂的分子，使离子进出脑细胞——包括神经元和神经胶质细胞。细胞外到细胞内离子梯度的改变对神经元放电有直接和间接的影响。例如，我们发现，当海马体切片暴露在低渗透性浸泡介质中时，细胞不仅膨胀，而且抑制性中间神经元中延迟整流钾电流的振幅也显著增加——这种效应可能有助于与低渗透性治疗相关的组织兴奋性增加。相反，氯共转运体的拮抗剂，速尿或布美他尼，在体外和体内制剂中都能阻断癫痫样活性。这种抗癫痫作用可能是由于药物阻断氯离子共转运的能力。事实上，组织长期暴露于低水平的细胞外氯化物也有类似的作用。这些实验表明，操纵离子平衡不仅可能促进癫痫样活动，而且可能为阻断癫痫发作的新治疗策略提供见解。(C) 1998 Elsevier Science B.V.版权所有
The majority of modern epilepsy research has focused on possible abnormalities in synaptic and intrinsic neuronal properties-as likely epileptogenic mechanisms as well as the targets for developing novel antiepileptic treatments. However, many other processes in the central nervous system contribute to neuronal excitability and synchronization. Regulation of ionic balance is one such set of critical processes, involving a complex array of molecules for moving ions into and out of brain cells-both neurons and glia. Alterations in extracellular-to-intracellular ion gradients can have both direct and indirect effects on neuronal discharge. We have found, for example, that when hippocampal slices are exposed to hypo-osmotic bathing medium, the cells not only swell, but there is also a significant increase in the amplitude of a delayed rectifier potassium current in inhibitory interneurons-an effect that may contribute to the increase in tissue excitability associated with hypo-osmolar treatments. In contrast, antagonists of the chloride co-transporter, furosemide or bumetanide, block epileptiform activity in both in vitro and in vivo preparations. This antiepileptic effect is presumably due to the drugs' ability to block chloride co-transport. Indeed, prolonged tissue exposure to low levels of extracellular chloride have a parallel action. These experiments indicate that manipulation of ionic balance may not only facilitate epileptiform activities, but may also provide insight into new therapeutic strategies to block seizures. (C) 1998 Elsevier Science B.V. All rights reserved.