title: Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice.
abstract: Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction.
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: Artur A
authors.initials: AA
authors.lastname: Indzhykulian
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Niksch
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: Roxanna M
authors.initials: RM
authors.lastname: Webber
authors.affiliation: Department of Medicine, Division of Nephrology, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia-Gonzalez
authors.affiliation: Department of Medicine, Division of Nephrology, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Terry
authors.initials: T
authors.lastname: Watnick
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.|Department of Physiology, McGill University Montréal, Québec, Canada.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Vollrath
authors.affiliation: Department of Neurobiology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: David P
authors.initials: DP
authors.lastname: Corey
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D003051:Cochlea / Q000502:physiology; D007758:Ear, Inner / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006198:Hair Cells, Auditory / Q000502:physiology*; D006309:Hearing; D040542:Mechanotransduction, Cellular; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D018408:Patch-Clamp Techniques; D011956:Receptors, Cell Surface / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics*; D050396:TRPP Cation Channels / Q000235:genetics; D050051:Transient Receptor Potential Channels / Q000235:genetics*
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D050053:TRPM Cation Channels; D050396:TRPP Cation Channels; D050051:Transient Receptor Potential Channels; C512453:PKD1L3 protein, mouse; C486487:Pkd2l1 protein, mouse; C511305:Pkd2l2 protein, mouse; C544443:TRPM2 protein, mouse