MODULATION OF INTRACARDIAC NEURONS BY MAST CELLS

肥大细胞对心内神经元的调节

• 批准号: 2669715
• 负责人: JEAN C HARDWICK
• 金额: $ 8.87万
• 依托单位: ITHACA COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2669715
• 关键词: action potentials; calcitonin gene related peptide; electrophysiology; granule; guinea pigs; heart innervation; heart pharmacology; histamine; immunocytochemistry; leukotrienes; mast cell; membrane potentials; neuroimmunomodulation; parasympathetic nervous system; prostaglandins; substance P

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.

描述：心脏功能的控制是同情之间的平衡 和自主神经系统的副交感分支。 这个平衡 可以在某些条件下改变例如病理激活 免疫系统，例如对位于肥大细胞的过敏或局部刺激 心。 肥大细胞脱粒，组胺的释放和 其他活性分子会引起心脏功能的深刻变化。 这 该建议的主要目标是确定肥大细胞的效果 刺激和脱粒对副交感神经活动 心。 先前的工作显示了肥大细胞产品的直接作用，例如 心肌细胞，起搏器细胞和心肌上的组胺和类花生素 交感神经传入终端，而本提案中的研究是 首先检查对副交感神经途径的影响。 第一个具体目的旨在确定 抗原诱导的肥大细胞在膜特性上脱粒 灵敏的豚鼠心脏中的副交感神经后神经元。 来自敏化动物的组织将用于确定 反应中副交感神经元活性的电生理学变化 抗原诱导的肥大细胞脱粒。 要测量的参数 包括膜电位，输入电阻，动作电位 配置，兴奋性和快速神经节传输。 第二个目的是确定组胺，前列腺素和 副交感神经的活性和膜特性的白细胞 神经元。 对膜电位，输入电阻，作用的影响 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。 将进行研究以关联 记录的响应类型以及 心脏神经节内的副交感神经元，潜力 肽能输入（物质P，CGRP）或靠近心脏桅杆 细胞。