Adenosine and modulation of synaptic transmission

描述(摘自申请人的摘要)： 长期以来，他一直致力于确定脑出血的神经生物学机制 腺苷，首席研究员构建了一个新的假说 细胞内腺苷的释放不仅是因为 细胞内钙水平，也来自细胞内的酸化 环境，通过细胞内pH值的下降来衡量。这项建议 将主要使用海马片的制备来探索各种 从电生理学的角度研究腺苷神经生物学。 第一个目标将探索细胞内pH和钙在细胞中的作用 调节腺苷的释放。这些研究将探索是否会发生变化 细胞内钙和pH都是产生 使用各种影响细胞内腺苷释放的试剂 周围的环境。第二个具体目标是探索腺苷是否在 实验在调节神经元基本兴奋性中的作用 在腺苷A1受体基因敲除小鼠中。这些研究将确定 KO小鼠的海马片是过度兴奋的，腺苷的KO是否 A1受体影响其他抑制性受体的功能。

DESCRIPTION(From applicant's abstract): In his long-standing interests in determining neurobiological mechanisms of adenosine, the principal investigator has constructed a novel hypothesis that release of intracellular adenosine results not only from an increase in intracellular calcium levels but also from an acidification of intracellular milieu, as measured by an decrease in intracellular pH values. This proposal will predominately use the hippocampal slice preparation to explore various aspects of adenosine neurobiology from an electrophysiological point of view. The first aim will explore the role of intracellular pH and calcium in mediating adenosine release. These studies will explore whether changes in intracellular calcium and pH are both necessary and sufficient to produce adenosine release by using a variety of reagents which affect the intracellular milieu. The second specific aim explore whether adenosine plays an important role in regulating the basic excitability of neurons by performing experiments in adenosine A1 receptor-knockout mice. These studies will determine whether hippocampal slices from KO mice are hyperexcitable, and whether KO of adenosine A1 receptors affect the function of other inhibitory receptors.