Calcium-dependent glutamate release from astrocytes

描述（由申请人提供）：星形胶质细胞是神经胶质细胞的一种亚型，基于细胞内Ca2+变化表现出一种兴奋性。这些细胞内钙的变化，即，振荡可以由神经递质诱发。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的释放，我们假设钙振荡的频率也控制谷氨酸从这些细胞的释放量。我们将在《特定目标I》中检验这一假设。神经元中的钙依赖性分泌可以通过钙下游分泌机制的蛋白激酶A（PKA）和蛋白激酶C（PKC）依赖性磷酸化来调节。由于星形胶质细胞表达负责神经元分泌的分泌机制的核心蛋白，我们推测，从星形胶质细胞释放谷氨酸也可能是由PKA和PKC依赖的磷酸化在分泌机制的网站调制。我们将在具体目标II中检验这一假设。 具体目标一：我们将测试的假设，从星形胶质细胞释放谷氨酸是由钙振荡的频率控制。 具体目的II：我们将检验PKA和PKC调节星形胶质细胞钙依赖性谷氨酸释放的假设。 这项研究将为星形胶质细胞如何与神经元通信提供新的重要信息。由于星形胶质细胞通过释放谷氨酸来调节突触传递，因此对神经胶质细胞作用的新认识有可能改变我们对中枢神经系统功能和功能障碍的看法

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