ABSTRACT
The observation that cell bodies (somata) of primary sensory neurons are endowed with receptors similar to those that exist on their central or peripheral nerve terminals has been known for more than 30 years. Nishi et al.50 demonstrated that activation of GAB A receptors on somatosensory (dorsal root ganglion, DRG) neurons produced a membrane depolarization that is mediated by the efflux of chloride ions. From this observation, they proposed that the mechanism underlying GABA-evoked depolarization of primary afferent nerve terminals might also be due to an increase in chloride permeability. The correspondence between the chemosensitivity of vagal primary afferent nerve terminals and their cell bodies for a panel of excitatory/sensitizing substances and inflammatory mediators (serotonin, histamine, bradykinin, Substance P, and prostaglandins) was initially and elegantly delineated in a series of publications by Higashi and co-workers.24 These results were derived from intracellular recordings of primary vagal afferent cell bodies in intact vagal ganglia, in vitro. Working with intact ganglia it was possible to measure conduction velocities of the impaled neurons and thus to correlate somal chemosensitivity with a neuronal phenotype, conduction velocity. Type A neurons have axons with conduction velocities 6 to 12 m/sec and somal action potentials that are completely blocked by tetrodotoxin (TTX, 0.1 to 0.5 FM). Type C neurons that have axons with conduction velocities 0.3 to 1.4 m/sec and somal action potentials resistant to TTX (1 to 5 µM). These two classes of neurons are also distinguished by their sensitivity to inflammatory mediators. Type C neurons are depolarized by serotonin, bradykinin or histamine, while type A neurons are relatively insensitive to these mediators. One drawback of this preparation is that intact vagal ganglion contain many different cell types besides primary afferent somata. Satellite cells, endothelial cells, and immune cells (macrophages and mast cells) are present in primary sensory ganglia42 and may respond to inflammatory mediators and autacoids by releasing signal molecules that, in turn, alter the excitability of primary afferents.23 Thus, when studying the actions of autacoids on neurons in intact vagal ganglia, interpretation of their site-of-action can be compromised by the heterogeneity of the tissue.
