Calcium-dependent glutamate release from astrocytes

星形胶质细胞钙依赖性谷氨酸释放

• 批准号: 6822708
• 负责人: VLADIMIR PARPURA
• 金额: $ 29.66万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6822708
• 关键词: astrocytes; biological signal transduction; calcium flux; cell cell interaction; enzyme activity; flash photolysis; fluorescence microscopy; glutamate receptor; glutamates; laboratory rat; neural transmission; neurons; neuropharmacology; newborn animals; phosphorylation; protein kinase A; protein kinase C; receptor expression; secretion; single cell analysis; voltage /patch clamp

DESCRIPTION (provided by applicant): Astrocytes, a subtype of glial cell, exhibit a form of excitability based on intracellular Ca2+ variations. These intracellular calcium variations, i.e., oscillations can be evoked by neurotransmitters. The functional consequences of calcium oscillations in astrocytes are poorly understood. Since the level of intracellular calcium ions control glutamate release from astrocytes, we hypothesize that the frequency of calcium oscillations also control the amount of glutamate release from these cells. We will test this hypothesis in Specific Aim I. Calcium-dependent secretion in neurons can be modulated by the protein kinase A (PKA)- and protein kinase C (PKC)-dependent phosphorylation of secretory machinery downstream of calcium. Since astrocytes express the core proteins of the secretory machinery responsible for neuronal secretion, we hypothesize that glutamate release from astrocytes may also be modulated by PKA- and PKC-dependent phosphorylation at the site of secretory machinery. We will test this hypothesis in Specific Aim II. Specific Aim I: We will test the hypothesis that glutamate release from astrocytes is controlled by the frequency of calcium oscillations. Specific Aim Il: We will test the hypothesis that PKA and PKC modulate calcium-dependent glutamate release from astrocytes. This study will provide new and important information on how astrocytes communicate with neurons. Since astrocytes modulate synaptic transmission by releasing glutamate, this new insight into glial action has potential to change the way we think about central nervous system functions and dysfunctions

描述（由申请人提供）：星形胶质细胞是神经胶质细胞的亚型，表现出基于细胞内Ca2+变化的一种兴奋性。这些细胞内钙的变化，即，神经递质可以引起振荡。星形胶质细胞中钙振荡的功能后果知之甚少。由于细胞内钙离子的水平控制谷氨酸从星形胶质细胞释放，因此我们假设钙振荡的频率还控制了从这些细胞中释放谷氨酸的量。我们将在特定的目标I中检验该假设。神经元中钙依赖性分泌可以通过蛋白激酶A（PKA）和蛋白激酶C（PKC） - 钙下游分泌机械的磷酸化磷酸化的磷酸化磷酸化调节。由于星形胶质细胞表达了负责神经元分泌的分泌机制的核心蛋白质，因此我们假设从星形胶质细胞释放谷氨酸，也可以通过分泌机械部位的PKA-和PKC依赖性磷酸化来调节。我们将在特定目标II中检验这一假设。 特定目的I：我们将检验以下假设：从星形胶质细胞释放谷氨酸是由钙振荡频率控制的。 特定目的IL：我们将检验以下假设：PKA和PKC调节依赖性钙从星形胶质细胞中释放出来。 这项研究将提供有关星形胶质细胞如何与神经元沟通的新的重要信息。由于星形胶质细胞通过释放谷氨酸来调节突触传播，因此这种对神经胶质作用的新见解有可能改变我们考虑中枢神经系统功能和功能障碍的方式