Molecular biological and electrophyrsiological studies of extranodal matrices on the saltatory conduction of the optic nerve

Bral1/Hapln2蛋白在中枢神经系统的Ranvier结点特异表达，通过与透明质酸的稳定结合，对维持基质分子起重要作用。为了探讨结外基质在跳跃性传导中的作用，我们对Bral1/Hapln2基因敲除小鼠进行了分析。1.免疫组织化学和电子显微镜分析在由胶质细胞(少突胶质细胞)和神经元(轴突)相互作用组成的副神经节的形成上没有明显的变化。对Na+通道的聚集也没有明显的影响，而Na+通道是动作电位产生和信号传播所必需的。2.电泳学分析然而，当我们通过电生理测量比较动作电位在视神经上的传播速度时，野生型和Bral1/Hapln2缺陷小鼠之间有显著差异。为了找出这些差异，我们进一步研究了Diff…结外基质增多，星形胶质细胞内足附着于结节。在Bral1/Hapln2基因缺陷小鼠中，我们发现了几种ECM分子的错误定位，包括versican(一种硫酸软骨素蛋白多糖)和tenascin-R等。在这些分析中，我们可以发现一个ECM分子，到目前为止还没有报道定位在Ranvier的节点，与Bral1/Hapln2共定位并稳定。结外基质的可能生理作用通过神经胶质细胞和神经细胞的相互作用，在副神经节的形成和星形胶质细胞足突的形成上没有明显的差异。我们只能观察到结外矩阵结构的不同。因此，我们假设由硫酸软骨素蛋白多糖和其他糖蛋白组成的基质分子复合体有助于维持结节周围的微环境。可能，它可以作为一个Na+离子池，这对于通过节点电压依赖的Na+通道内流来产生动作电位是重要的。较少

The Bral1/Hapln2 proteins are expressed specifically at the nodes of Ranvier in the central nervous system and supposed to be important for the maintenance of matrix molecules by stable binding on the hyaluronan. To explore the role of the extranodal matrices on the saltatory conduction, we analyzed the Bral1/Hapln2 knockout mice.1.Immunohistochemical and electronmicroscopic analysisThere was no obvious alteration on the formation of paranodes, which is consisted of glial cell (oligodendrocyte) and neuron (axon) interactions. There was also no obvious effect on the clustering of Na+ channels, which is essential for the production of action potentials and propagation of the signals.2.Electrophiological analysisHowever, when we compared the speed of propagation of action potentials on the optic nerves via electrophysiological measurement, there was a significant difference between wild type and Bral1/Hapln2 deficient mice. To figure out those differences, we investigated further the diff … More erences of the extranodal matrices as well as the attachment of the endofoot of astrocyte at the node. We could find the mislocalization of several ECM molecules including versican (a chondroitin sulfate proteoglycan), tenascin-R and others in the Bral1/Hapln2 deficient mice. During those analyses, we could find one ECM molecule, which has not reported so far to localize at the nodes of Ranvier, is colocalizing and stabilized with Bral1/Hapln2. Nevertheless, there was no obvious difference of the attachment of the endofoot of the astrocyte.3.Possible physiological roles of the extranodal matrixCollectively, there was no obvious difference in formation of paranodes and astrocyte foot process via glial and neuronal cell interactions. We could only observe the difference in the formation of the structure of extranodal matrices. Therefore, we assume that the complex of matrix molecules consisting of chondroitin sulfate proteoglycans and other glycoprotein is contributing to the maintenance of the microenvironment around the nodes. Possibly, it can serve as a Na+ ion-pool, which is important for generating the action potentials via influx through the voltage dependent Na+ channels at the nodes. Less