MODULATION OF INTRACARDIAC NEURONS BY MAST CELLS

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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.