title: Kv1.1 channels act as mechanical brake in the senses of touch and pain.
abstract: Molecular determinants of threshold sensitivity of mammalian mechanoreceptors are unknown. Here, we identify a mechanosensitive (MS) K(+) current (IKmech) that governs mechanical threshold and adaptation of distinct populations of mechanoreceptors. Toxin profiling and transgenic mouse studies indicate that IKmech is carried by Kv1.1-Kv1.2 heteromers. Mechanosensitivity is attributed to Kv1.1 subunits, through facilitation of voltage-dependent open probability. IKmech is expressed in high-threshold C-mechano-nociceptors (C-HTMRs) and Aβ-mechanoreceptors, but not in low-threshold C-mechanoreceptors. IKmech opposes depolarization induced by slow/ultraslow MS cation currents in C-HTMRs, thereby shifting mechanical threshold for firing to higher values. However, due to kinetics mismatch with rapidly-adapting MS cation currents, IKmech tunes firing adaptation but not mechanical threshold in Aβ-mechanoreceptors. Expression of Kv1.1 dominant negative or inhibition of Kv1.1/IKmech caused severe mechanical allodynia but not heat hyperalgesia. By balancing the activity of excitatory mechanotransducers, Kv1.1 acts as a mechanosensitive brake that regulates mechanical sensitivity of fibers associated with mechanical perception.
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Boulevard Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Jizhe
authors.initials: J
authors.lastname: Hao
authors.forename: Françoise
authors.initials: F
authors.lastname: Padilla
authors.forename: Mathieu
authors.initials: M
authors.lastname: Dandonneau
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Florian
authors.initials: F
authors.lastname: Lesage
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D051638:Ether-A-Go-Go Potassium Channels / Q000502:physiology; D006930:Hyperalgesia / Q000503:physiopathology; D007150:Immunohistochemistry; D051656:KCNQ Potassium Channels / Q000502:physiology; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000502:physiology*; D008465:Mechanoreceptors / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014110:Touch / Q000502:physiology*
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D051656:KCNQ Potassium Channels; C496885:Kcnh1 protein, mouse; D024681:Potassium Channels, Calcium-Activated; D051662:Kv1.1 Potassium Channel