title: TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.
abstract: Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea.
authors.affiliation: Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Center for Life Sciences 12251, Boston, MA 02115, USA.
authors.forename: Bifeng
authors.initials: B
authors.lastname: Pan
authors.forename: Gwenaelle S
authors.initials: GS
authors.lastname: Géléoc
authors.forename: Yukako
authors.initials: Y
authors.lastname: Asai
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Horwitz
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kurima
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
mesh_terms: D000161:Acoustic Stimulation; D000256:Adenoviridae / Q000235:genetics; D000367:Age Factors; D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009925:Organ of Corti / Q000166:cytology; D018408:Patch-Clamp Techniques; D014161:Transduction, Genetic
chemical_list: D008565:Membrane Proteins; C514628:TMC1 protein, mouse; C575755:TMC2 protein, mouse; D002118:Calcium