Calcium-dependent glutamate release from astrocytes

描述（申请人提供）：星形胶质细胞，胶质细胞的一种亚型，表现出一种基于细胞内Ca2+变化的兴奋性。这些细胞内钙的变化，即振荡可以由神经递质引起。星形胶质细胞中钙振荡的功能后果尚不清楚。由于细胞内钙离子水平控制着星形胶质细胞中谷氨酸的释放，我们假设钙振荡的频率也控制着这些细胞中谷氨酸的释放量。我们将在《特异性目的1》中验证这一假设。神经元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，我们假设星形胶质细胞的谷氨酸释放也可能受到分泌机制部位PKA-和pkc依赖性磷酸化的调节。我们将在具体目标II中检验这一假设。

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