title: TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.
abstract: Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Youtian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Fei
authors.initials: F
authors.lastname: Ru
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Marian
authors.initials: M
authors.lastname: Kollarik
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland syyu@jhmi.edu.
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Yu
mesh_terms: D000200:Action Potentials; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D020013:Calcium Signaling; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000294:innervation*; D006168:Guinea Pigs; D008297:Male; D008610:Menthol / Q000031:analogs & derivatives / Q000494:pharmacology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012677:Sensation; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000813:Anilides; D001549:Benzamides; C532415:N-(3-aminopropyl)-2-(((3-methylphenyl) methyl)oxy)-N-(2-thienylmethyl)benzamide hydrochloride salt; C533807:N-(4-methoxyphenyl)-4-menthone-3-carboxamide; D012333:RNA, Messenger; D050053:TRPM Cation Channels; D050916:TRPV Cation Channels; D013876:Thiophenes; D008610:Menthol
keywords: C fiber; TRPM8; esophagus; menthol; vagal