title: KCNQ4 K(+) channels tune mechanoreceptors for normal touch sensation in mouse and man.
abstract: Mutations inactivating the potassium channel KCNQ4 (K(v)7.4) lead to deafness in humans and mice. In addition to its expression in mechanosensitive hair cells of the inner ear, KCNQ4 is found in the auditory pathway and in trigeminal nuclei that convey somatosensory information. We have now detected KCNQ4 in the peripheral nerve endings of cutaneous rapidly adapting hair follicle and Meissner corpuscle mechanoreceptors from mice and humans. Electrophysiological recordings from single afferents from Kcnq4(-/-) mice and mice carrying a KCNQ4 mutation found in DFNA2-type monogenic dominant human hearing loss showed elevated mechanosensitivity and altered frequency response of rapidly adapting, but not of slowly adapting nor of D-hair, mechanoreceptor neurons. Human subjects from independent DFNA2 pedigrees outperformed age-matched control subjects when tested for vibrotactile acuity at low frequencies. This work describes a gene mutation that modulates touch sensitivity in mice and humans and establishes KCNQ4 as a specific molecular marker for rapidly adapting Meissner and a subset of hair follicle afferents.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Heidenreich
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Lechner
authors.forename: Vitya
authors.initials: V
authors.lastname: Vardanyan
authors.forename: Christiane
authors.initials: C
authors.lastname: Wetzel
authors.forename: Cor W
authors.initials: CW
authors.lastname: Cremers
authors.forename: Els M
authors.initials: EM
authors.lastname: De Leenheer
authors.forename: Gracia
authors.initials: G
authors.lastname: Aránguez
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Moreno-Pelayo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Jentsch
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
mesh_terms: D000328:Adult; D000818:Animals; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics* / Q000378:metabolism; D008465:Mechanoreceptors / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D012684:Sensory Thresholds / Q000502:physiology; D014110:Touch / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology*
chemical_list: D051656:KCNQ Potassium Channels; C492167:Kcnq4 protein, mouse
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