Bliznyuk Alice, Gradwohl Gideon, Hollmann Michael, Grossman Yoram
Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev Beer-sheva, Israel.
Department of Physics, Jerusalem College of Technology Jerusalem, Israel.
Front Mol Neurosci. 2016 Jun 10;9:40. doi: 10.3389/fnmol.2016.00040. eCollection 2016.
Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with central nervous system (CNS) hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. Our laboratory has reported differential current responses under HP conditions in NMDAR subtypes that contain either GluN1-1a or GluN1-1b splice variants co-expressed in Xenopus laevis oocytes with all four GluN2 subunits. Recently, we reported that the increase in ionic currents measured under HP conditions is also dependent on which of the eight splice variants of GluN1 is co-expressed with the GluN2 subunit. We now report that the NMDAR subtype that contains GluN1-4a/b splice variants exhibited "dichotomic" (either increased or decreased) responses at HP. The distribution of the results is not normal thus analysis of variance (ANOVA) test and clustering analysis were employed for statistical verification of the grouping. Furthermore, the calculated constants of alpha function distribution analysis for the two groups were similar, suggesting that the mechanism underlying the switch between an increase or a decrease of the current at HP is a single process, the nature of which is still unknown. This dichotomic response of the GluN1-4a/b splice variant may be used as a model for studying reduced response in NMDAR at HP. Successful reversal of other NMDAR subtypes response (i.e., current reduction) may allow the elimination of the reversible malfunctioning short term effects (HPNS), or even deleterious long term effects induced by increased NMDAR function during HP exposure.
职业深水潜水员暴露于1.1兆帕以上的高压环境中时，会患上高压神经综合征（HPNS），该综合征与中枢神经系统（CNS）的过度兴奋有关。此前有报道称，高压会增强N-甲基-D-天冬氨酸受体（NMDAR）的突触反应，增加神经元兴奋性，并可能导致不可逆的神经元损伤。我们实验室报告了在高压条件下，含有GluN1-1a或GluN1-1b剪接变体并与所有四个GluN2亚基共表达于非洲爪蟾卵母细胞中的NMDAR亚型的不同电流反应。最近，我们报告称，在高压条件下测量到的离子电流增加也取决于与GluN2亚基共表达的GluN1的八个剪接变体中的哪一个。我们现在报告，含有GluN1-4a/b剪接变体的NMDAR亚型在高压下表现出“二分法”（增加或减少）反应。结果分布不正常，因此采用方差分析（ANOVA）测试和聚类分析对分组进行统计验证。此外，两组的α函数分布分析计算常数相似，这表明高压下电流增加或减少之间转换的潜在机制是一个单一过程，其本质仍然未知。GluN1-4a/b剪接变体的这种二分法反应可作为研究高压下NMDAR反应降低的模型。成功逆转其他NMDAR亚型的反应（即电流降低）可能会消除可逆的短期功能失调效应（HPNS），甚至消除高压暴露期间NMDAR功能增加所诱导的有害长期效应。
