title: Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ihcurrents.
abstract: The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In this study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers. We found that SA1 responses were potentiated by serotonin at low concentration (10 μM) but almost completely occluded by serotonin at high concentration (2 mM). In contrast, SA1 responses were not significantly affected by ATP and its metabolically stable analog α,β-methylene-ATP, glutamate, γ-aminobutyric acid (GABA), and histamine. SA1 responses were also not affected by antagonists for P2X receptors, ionotropic glutamate receptors, and ionotropic GABA and glycine receptors. Whole-cell patch-clamp recordings reconfirm the presence of both ionotropic and metabotropic 5-HT receptors on afferent neurons and their terminals innervating whisker hair follicles. All whisker afferent neurons expressed hyperpolarization-activated inward currents (Ih), which are potentiated by serotonin through the activation of metabotropic 5-HT receptors. Taken together, the findings substantiate the serotonergic mechanism of tactile transmission at Merkel discs and identify the involvement of Ihcurrents in postsynaptic excitatory actions of serotonin. In addition, the findings do not favor any significant involvement of ATP, glutamate, histamine, GABA, or glycine in tactile transmission at the Merkel discs of whisker hair follicles.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Weipang
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kanda
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ikeda
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ling
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jianguo G
authors.identifier: 0000-0002-8404-9850
authors.initials: JG
authors.lastname: Gu
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018862:Merkel Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology; D018408:Patch-Clamp Techniques; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; C577833:Abca1 protein, mouse
keywords: 5-HT receptors; Merkel cells; serotonin; touch; whisker hair follicles