title: The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes.
abstract: Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%-95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65-75%). ASIC1, ASIC2, and ASIC3 were expressed in 65-75%, 55-70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathophysiology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dusenkova
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland;
authors.forename: Fei
authors.initials: F
authors.lastname: Ru
authors.affiliation: Department of Pathophysiology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Lenka
authors.initials: L
authors.lastname: Surdenikova
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Institute of Anatomy and Cell Biology-Cardiopulmonary Neurobiology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Nassenstein
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Jozef
authors.initials: J
authors.lastname: Hatok
authors.affiliation: Department of Biochemistry, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia; Department of Urology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Robert
authors.initials: R
authors.lastname: Dusenka
authors.affiliation: Department of Gastroenterology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Peter
authors.initials: P
authors.lastname: Banovcin
authors.affiliation: Department of Urology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Jan
authors.initials: J
authors.lastname: Kliment
authors.affiliation: Department of Pathophysiology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia;
authors.forename: Milos
authors.initials: M
authors.lastname: Tatar
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathophysiology, Comenius University in Bratislava, Jessenius Faculty of Medicine, Martin, Slovakia; kollarik@jhmi.edu.
authors.forename: Marian
authors.initials: M
authors.lastname: Kollarik
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004947:Esophagus / Q000294:innervation*; D006168:Guinea Pigs; D051379:Mice; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D009928:Organ Specificity; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D062565:Acid Sensing Ion Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D050916:TRPV Cation Channels
keywords: acid-sensing ion channels; afferent; esophagus; vagus nerve