glyr甘氨酸受体的学习教案.pptxVIP

glyr甘氨酸受体的学习教案第1页/共6页 A model for activity-dependent GlyR clustering at developing postsynaptic membrane specializationsA glycinergic presynaptic terminal and a segment of the plasma membrane of a GlyR-expressing postsynaptic neuron are shown at different stages of synaptogenesis.Kneussel M , Betz H J Physiol 2000;525:1-9?2000 by The Physiological SocietyA, immature stage: GlyRs are randomly distributed in the plasma membrane of the postsynaptic cell, whereas gephyrin is cytoplasmically localized.第2页/共6页 aaaB, initiation of gephyrin cluster formation桥蛋白成簇构造: release of glycine from the presynaptic terminal gates neighbouring GlyRs. This results in a depolarizing去极化 Cl? efflux流出 (downward arrows) that activates nearby voltage-dependent Ca2+ channels. The resultant local microdomain of elevated Ca2+ concentration triggers the membrane apposition and aggregation 加入以及聚集of gephyrin at sites of GlyR activation.第3页/共6页 aaC, maturation stage成熟阶段: the growing submembraneous gephyrin aggregate traps additional GlyRs underneath the presynaptic terminal and immobilizes固定 the receptors in the developing postsynaptic membrane by anchoring them to the subsynaptic cytoskeleton. Due to a change in Cl? equilibrium potential, GlyR activation triggers Cl? influx causing hyperpolarization (upward arrows), and thus inhibition of neuronal firing. This model is based on data by Kirsch Betz (1998) and does not include G protein-mediated signalling pathways that may also contribute to the clustering process (Kins et al. 2000).第4页/共6页 Gly对细胞内钙的激动剂诱导的增加的抑制的假定机理，经由IP3/Ca2+ pathway。受体介导的PLCβ激活使IP3增加，有助于大量活性Ca2+从内质网中释放经由IP3受体。细胞内Ca2+的变化激活电压依赖Ca2+门控通道，导致细胞外Ca2+的大量内流，进而作为第二信使激活NADPH氧化酶，结果通过活化NF-κB使多种细胞因子的表达。 简单的说，PGE2, ROS, and cytokines的产生对肝脏是有害的。Gly减弱细胞内信号以及细胞因子的生成，通过对电压依赖Ca2+门控通道的超极化诱导抑制。. Ga, activated G-protein; ER, endoplasmic reticulum; PLCβ, phospholipase Cβ; IP3, inositol 1,4,5-triphosphate; PIP2, phosphatidylinositol 4,5- biphosphate; PLA2, phospholipase A2; NF-κB, nuclear factor kappa