Regulation of parasympathetic neurons by mast cells and histamine in the guinea pig heart

The potential interaction between the immune system and the autonomic nervous system was examined in the cardiac ganglia of guinea pigs. Intracellular voltage recordings were used to determine the effects of mast cell degranulation on the membrane properties of parasympathetic neurons in animals actively sensitized to ovalbumin. Stimulation of mast cell degranulation by perfusion with ovalbumin (10 μg/ml) produced a depolarization and increase in the excitability of intracardiac neurons. These effects could be mimicked by histamine application, either by perfusion (10 μM) or by local pressure application (100 μM, 1-2 s application). In either case, histamine application resulted in a similar membrane depolarization and increase in excitability. Immunohistochemical experiments demonstrated that histamine-immunoreactive mast cells are located in close proximity to parasympathetic postganglionic neurons. The histamine response was not due to release of other neurotransmitters from adjacent nerve terminals and both the depolarization and increase in excitability were inhibited by the H antagonist, pyrilamine (300 nM), and were unaffected by the H antagonist cimetidine (5 μM). Incubation of cardiac ganglion preparations from sensitized animals with pyrilamine prior to ovalbumin perfusion resulted in the inhibition of both the depolarization and increase in excitability. These results demonstrate that mast cell degranulation, and the subsequent release of histamine, results in the stimulation of intracardiac neurons via the activation of H receptors. Thus, local inflammatory reactions in the cardiac tissue can lead to the rapid activation of parasympathetic neurons, thereby altering cardiac function. Copyright © 2001 Elsevier Science B.V. 1 2