REGULATION OF CELLULAR EXCITABILITY BY STRESS HORMONES

描述：（改编自研究者摘要） 申请人最近提出的证据表明， 嗜铬细胞是由应激激素调节的， 下丘脑垂体肾上腺轴拟议的研究将进一步测试和 测量连接应力轴和急性心肌梗死力学的机制 肾上腺素反应证据表明类固醇应激激素 控制一个关键离子通道BK型钾离子通道的组装。通过 偏向前信使RNA的选择性剪接，激素“调整” 通道的结构，以增加通道的容易性的方式， 打开这导致细胞的兴奋性和肾上腺素增加 分泌物本研究将采用分子生物学（RT-PCR和 免疫细胞化学）和电生理（膜片钳）技术， 平行测量应激激素对结构和功能的影响， BK频道体内和体外的手术和激素扰动将 鉴定调节信号转导的分子途径，和 探索对细胞功能的影响。这项研究得益于 相同的分析可以应用于牛和大鼠细胞之间的比较， 在具有不同应激反应特征的大鼠品系之间，以及在大鼠品系之间， 发育阶段，以及实验处理组之间。 因此，我们的目标是阐明应激的分子机制， 经验，生命阶段和基因适应和/或限制的机制 儿茶酚胺分泌

DESCRIPTION: (Adapted from the Investigator's Abstract) The applicant recently presented evidence that the intrinsic excitability of chromaffin cells is regulated by stress hormones of the hypothalamic-pituitary-adrenal axis. The proposed study will further test and measure the mechanism linking the stress axis to the mechanics of acute epinephrine responses. The evidence suggests that steroid stress hormones control the assembly of a key ion channel, the BK-type potassium channel. By biasing the alternative splicing of pre-messenger RNA, the hormones "tune" the channel's structure in a way that increases the ease with which the channel is opened. This results in an increase in the cell's excitability and epinephrine secretion. This study will use molecular biological (RT-PCR and immunocytochemistry) and electrophysiological (patch clamp) techniques in parallel to measure the effects of stress hormones on structure and function of the BK channel. Surgical and hormonal perturbations in vivo and in vitro will identify molecular pathways by which the regulatory signal is transduced, and explore the consequences to cell function. The study benefits from the fact that the same assays can be applied to compare between bovine and rat cells, between rat strains with different stress response profiles, and between rat developmental stages, in addition to between experimental treatment groups. Thus, the goal is to elucidate molecular mechanisms by which stress experiences, life stages, and genes adapt and/or limit the mechanisms of catecholamine secretion.