CELL EXCITABILITY MECHANISMS OF ELECTROMAGNETIC FIELDS

描述：(改编自申请人的摘要)：公众关注 提出了电力线(60赫兹)可能产生的不利影响 神经系统上的电磁场(EMF)。我们的研究将 通过确定和检查以下机制来解决这个问题 电磁场在细胞、亚细胞和分子水平上影响神经细胞 从而改变关键的细胞功能。分离的肾上腺嗜铬细胞 将被用作交感神经系统功能的体外模型 这些研究。在初步实验中，将嗜铬细胞暴露在磁性环境中 0.8-1.4毫秒(Mt)范围内的磁通密度导致了 细胞内钙离子和一种刺激儿茶酚胺的释放。这些 在拟议的研究中，将进一步研究电动势诱导的效应。 研究将使用荧光钙成像技术和45Ca2 摄取测量以阐明电磁场诱导的机制 细胞内钙的增加。这两种相同的方法，在 高效液体联用测定儿茶酚胺 (高效液相色谱法)，将被用来建立长期效应的 电磁场对儿茶酚胺释放及儿茶酚胺生物合成的影响 将会被确定。这些研究将使用高效液相色谱和放射性同位素。 细胞内儿茶酚胺及其受体水平的标记方法 前体，原位和体外分析，以评估活性的变化 儿茶酚胺生物合成酶及分子生物学技术研究 酪氨酸羟基酶表达水平的变化，该酶是 催化儿茶酚胺生物合成途径中的限速步骤。 提出的研究的长期意义是重要的 将获得的关于电磁场对细胞的影响的信息 神经细胞。这些信息将是评估潜力的关键 与电磁场暴露相关的健康风险，以及帮助我们的 了解使用电磁场的潜在治疗策略。

DESCRIPTION: (Adapted from the applicant's abstract): Public concern has been raised about possible adverse effects of powerline (60-Hertz) electromagnetic fields (EMFs) on the nervous system. Our research will address this question by identifying and examining the mechanisms by which EMFs effect neural cells at the cellular, subcellular and molecular levels and thus alter key cellular functions. Isolated adrenal chromaffin cells will be used as an in vitro model of sympathetic nervous system function for these studies. In preliminary experiments, exposing chromaffin to magnetic flux densities in the 0.8 - 1.4 millitesla (mT) range caused both a rise in intracellular calcium and a stimulation catecholamine release. These EMF-induced effects will be further investigated in the proposed research. Studies will employ fluorescence calcium imaging techniques and 45Ca2+ uptake measurements to elucidate the mechanisms that underlie EMF-induced increases in intracellular calcium. These same two methodologies, in conjunction with assay of catecholamines by high performance liquid chromatography (HPLC), will be used to establish the long-term effects of EMFs on catecholamine release as well as catecholamine biosynthesis rates will be determined. These studies will employ HPLC and radioisotopic labeling methods to assess intracellular levels of catecholamines and their precursors, in situ and in vitro assays to assess alterations in activity of catecholamine biosynthetic enzymes and molecular biology techniques to study changes in the level of expression of tyrosine hydroxylase, the enzyme that catalyzes the rate-limiting step in the catecholamine biosynthetic pathway. The long-term significance of the proposed research is the important information that will be obtained regarding cellular effects of EMFs on neural cells. Such information will be essential for evaluating potential health risks associated with EMF exposure, as well as aiding our understanding of potential therapeutic strategies employing EMFs.