MODULATION OF INTRACARDIAC NEURONS BY MAST CELLS

描述：心脏功能的控制是交感神经之间的平衡 和自主神经系统的副交感神经分支。 这种平衡 在某些条件下，如病理性激活 免疫系统，例如过敏性或局部刺激肥大细胞位于 心脏 肥大细胞脱颗粒，释放组胺， 其他活性分子引起心脏功能的深刻变化。 的 这项建议的主要目标是确定肥大细胞的影响， 刺激和脱粒对副交感神经活动的影响 心 以前的工作已经表明肥大细胞产物的直接作用， 组胺和类花生酸对心肌细胞、起搏细胞和 交感神经传入终端，而在这项建议的研究是 首先检查对副交感神经通路的影响。 第一个具体目标是确定 抗原诱导的肥大细胞脱颗粒对细胞膜性质的影响 致敏豚鼠心脏的副交感节后神经元。 致敏动物的组织将用于测定 反应时副交感神经元活动的电生理变化 抗原诱导的肥大细胞脱颗粒 待测参数 包括膜电位、输入电阻、动作电位 构型、兴奋性和快速神经节传递。 第二个目的是确定组胺、甘草素和 白三烯对副交感神经活性和膜特性的影响 神经元 对膜电位、输入电阻、动作电位的影响 潜在的配置，兴奋性和突触前的功能 将研究副交感神经纤维。 将进行研究， 记录的响应类型以及 心神经节内的副交感神经元， 肽能输入（P物质，CGRP）或接近心脏肥大 细胞

DESCRIPTION: Control of cardiac function is a balance between sympathetic and parasympathetic branches of the autonomic nervous system. This balance can be altered under certain conditions such as pathologic activation of the immune system, e.g. allergic or local stimulation of mast cells located in the heart. Degranulation of mast cells with the release of histamine and other active molecules causes profound changes in cardiac function. The major goal of this proposal is to determine the effect of mast cell stimulation and degranulation on parasympathetic neural activity within the heart. Previous work has shown direct actions of mast cell products such as histamine and eicosanoids on cardiac myocytes, pacemaker cells and sympathetic afferent terminals, while the studies in this proposal are the first to examine effects on the parasympathetic pathway. The first specific aim is designed to determine the effect of antigen-induced mast cell degranulation on membrane properties of parasympathetic postganglionic neurons in the sensitized guinea pig heart. Tissue from sensitized animals will be used to determine the electrophysiological changes in parasympathetic neuron activity in response to antigen-induced mast cell degranulation. The parameters to be measured include membrane potential, input resistance, action potential configuration, excitability, and fast ganglionic transmission. The second aim is to determine the effect of histamine, prostaglandins and leukotrienes on the activity and membrane properties of parasympathetic neurons. The effect on membrane potential, input resistance, action potential configuration, excitability, and the function of presynaptic parasympathetic fibers will be studied. Studies will be done to correlate the types of responses recorded and either the location of the parasympathetic neurons within the cardiac ganglion, the potential peptidergic inputs (substance P, CGRP) or the proximity to cardiac mast cells.