HISTAMINE RELEASE FROM BEIGE MOUSE MAST CELLS

米色小鼠肥大细胞释放组胺

• 批准号: 3897034
• 负责人: J ZIMMERBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3897034
• 关键词: cell fusion; cell membrane; electron microscopy; exocytosis; extracellular matrix; granule; histamine release; intracellular; laboratory mouse; mast cell; secretion; voltage /patch clamp

Mast cells of the beige mouse contain large intracellular secretory granules (approximately 4 microns in diameter) whose membranes fuse with the plasma membrane in a process called exocytosis. During membrane fusion an exocytotic pore forms which connects the granule interior with the extracellular medium. Through the exocytotic pore the granule contents are released extracellularly and are free to diffuse to target cells. We have correlated electrophysiological and light microscopic data to investigate the structure of this exocytotic pore during secretion in mast cells from Beige mice. The time course for the widening of the pore is highly variable: it can widen quickly or slowly and can fluctuate between dilated and contracted states of variable conductance (flickering). Initial pore sizes are broadly distributed indicating that this pore is different from traditional membrane channels which have a relatively fixed conductance. The frequency histogram for occurrence of pores of given conductance is broad with a primary peak between 1 and 4 nS, indicating that pore size does not increase in quantal steps. A secondary maximum occurs at about 30 nS. We have searched fast-frozen, freeze-fracture replicas of rat mast cells and identified pores with small lumens. The 30 nS pores may represent the smallest pores seen in transmission electron microscopy. A model describing fusion on the molecular level which can account for the variable pore sizes, flickering, and known volumes of activation is described. In a second project isolated matrices of the giant secretory vesicles of Beige mouse mast cells were examined to determine the effects of the ionic composition of the bathing solution on their size. In general multivalent cations condense the matrix relative to univalents.

米色小鼠的肥大细胞含有大量的细胞内分泌 颗粒（直径约4微米），其膜与 在一个叫做胞吐作用的过程中破坏质膜。在膜融合期间 胞吐孔形成，其将颗粒内部与 细胞外介质通过胞吐孔， 在细胞外释放并自由扩散到靶细胞。 我们将电生理学和光学显微镜数据相关联， 研究肥大细胞分泌过程中该胞吐孔的结构 来自Beige小鼠的细胞。孔隙变宽的时间过程为 高度可变：它可以快速或缓慢地扩大，并可以在 可变电导的扩张和收缩状态（闪烁）。初始 孔隙大小广泛分布，表明该孔隙是不同的 传统的膜通道具有相对固定的 电导给出的孔隙出现频率直方图 电导宽，主峰在1和4 nS之间，表明 孔径不会以量子阶跃增加。次极大值 发生在30 nS左右。我们已经搜索了快速冷冻，冷冻断裂 大鼠肥大细胞的复制品，并确定了具有小管腔的孔。的30 nS孔可以代表透射电子显微镜中看到的最小孔。 显微镜一个在分子水平上描述聚变的模型， 考虑到可变的孔径，闪烁，和已知的体积 激活被描述。 在第二个项目中， 检查米色小鼠肥大细胞以确定离子型 沐浴液的组成对它们的大小。一般多价 阳离子相对于单价离子使基质缩合。