Immunologically induced neuromodulation of guinea pig nodose ganglion neurons.
The influence of specific antigen challenge on the excitability of C-cells in nodose ganglia isolated from actively sensitized guinea pigs was evaluated using intracellular recording techniques. Antigen (ovalbumin) caused a significant depolarization (approximately 8 mV) of the resting membrane potential. Antigen exposure had differing effects on the membrane input impedance; decreasing it in 15 neurons, increasing it in 6 neurons, and having no effect in 8 neurons. About 20% of guinea pig nodose C-cells reveal a long-lasting after-spike hyperpolarization (AHPslow). Antigen challenge reversibly blocked the AHPslow in 4 of 18 neurons studied in 18 ganglia. About 30% of the nodose ganglion neurons display a time- and voltage-dependent inward rectification at membrane potentials more negative than -75 mV. Exposing the ganglion to the sensitizing antigen consistently blocked this response in 8 of 8 neurons. Histological assessment of toluidine blue stained cells revealed that the nodose ganglion contained approximately 100 mast cells. Exposing the ganglion to ovalbumin stimulated mast cell degranulation, as measured by a decrease in number of stained cells, and evoked the release of histamine, PGD2, and immunoreactive peptidoleukotrienes from the tissue. The results support the hypothesis that endogenous inflammatory mediators released during the immediate hypersensitivity (allergic) reactions can modulate the excitability of primary C-fiber afferents. Mechanisms underlying antigen-induced neuromodulation of these neurons include depolarization of the resting membrane potential, changes in membrane resistance, blockade of a time- and voltage-dependent anomalous rectifier, and, in some cells, blockade of the AHPslow.
Undem
B J
BJ
Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, Maryland.
Hubbard
W
W
Weinreich
D
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D005726:Ganglia, Parasympathetic / Q000166:cytology*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007114:Immunization; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D015213:Neuroimmunomodulation; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D014630:Vagus Nerve / Q000166:cytology*
D000941:Antigens; D015289:Leukotrienes; D011453:Prostaglandins; D010047:Ovalbumin