title: Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat.
abstract: The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type.
authors.affiliation: Oregon Health & Science University, Department of Physiology and Pharmacology, 3181 Sam Jackson Park Road, Mailcode: L334, Portland, OR 97239-3098, United States.
authors.forename: Sam M
authors.initials: SM
authors.lastname: Hermes
authors.affiliation: Oregon Health & Science University, Department of Physiology and Pharmacology, 3181 Sam Jackson Park Road, Mailcode: L334, Portland, OR 97239-3098, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
authors.affiliation: Oregon Health & Science University, Department of Physiology and Pharmacology, 3181 Sam Jackson Park Road, Mailcode: L334, Portland, OR 97239-3098, United States. Electronic address: aichers@ohsu.edu.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Aicher
mesh_terms: D000818:Animals; D002772:Cholera Toxin / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D050916:TRPV Cation Channels / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D037102:Lectins; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002772:Cholera Toxin
keywords: Cholera toxin B subunit; Confocal microscopy; Isolectin B4; P2X3; TRPV1; Vagus nerve