Adenosine and modulation of synaptic transmission

描述（来自申请人摘要）： 他长期致力于确定神经生物学机制， 腺苷，首席研究员构建了一个新的假设， 细胞内腺苷的释放不仅是由于 细胞内钙离子水平，而且从细胞内的酸化 细胞内pH值的降低，如通过细胞内pH值的降低所测量的。这项建议 将主要使用海马切片制备来探索各种 腺苷神经生物学方面从电生理学的观点。 第一个目标将探讨细胞内pH值和钙离子的作用， 介导腺苷释放。这些研究将探讨 细胞内钙和pH都是必需的，并且足以产生 腺苷释放通过使用各种试剂，影响细胞内 环境。第二个具体目标是探索腺苷是否在 在调节神经元基本兴奋性方面的作用 腺苷A1受体敲除小鼠中。这些研究将确定是否 KO小鼠的海马切片是过度兴奋的， 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.