title: Transient receptor potential melastatin 1: a hair cell transduction channel candidate.
abstract: Sound and head movements are perceived through sensory hair cells in the inner ear. Mounting evidence indicates that this process is initiated by the opening of mechanically sensitive calcium-permeable channels, also referred to as the mechanoelectrical transducer (MET) channels, reported to be around the tips of all but the tallest stereocilia. However, the identity of MET channel remains elusive. Literature suggests that the MET channel is a non-selective cation channel with a high Ca(2+) permeability and ~100 picosiemens conductance. These characteristics make members of the transient receptor potential (TRP) superfamily likely candidates for this role. One of these candidates is the transient receptor potential melastatin 1 protein (TRPM1), which is expressed in various cells types within the cochlea of the mouse including the hair cells. Recent studies demonstrate that mutations in the TRPM1 gene underlie the inherited retinal disease complete congenital stationary night blindness in humans and depolarizing bipolar cell dysfunction in the mouse retina, but auditory function was not assessed. Here we investigate the role of Trpm1 in hearing and as a possible hair cell MET channel using mice homozygous for the null allele of Trpm1 (Trpm1(-/-)) or a missense mutation in the pore domain of TRPM1 (Trpm1(tvrm27/tvrm27)). Hearing thresholds were evaluated in adult (4-5 months old) mice with auditory-evoked brain stem responses. Our data shows no statistically significant difference in hearing thresholds in Trpm1(-/-) or Trpm1(tvrm27/tvrm27) mutants compared to littermate controls. Further, none of the mutant mice showed any sign of balance disorder, such as head bobbing or circling. These data suggest that TRPM1 is not essential for development of hearing or balance and it is unlikely that TRPM1 is a component of the hair cell MET channel.
authors.affiliation: Otolaryngology Head and Neck Surgery, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Gerka-Stuyt
authors.forename: Adrian
authors.initials: A
authors.lastname: Au
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
authors.forename: Kumar N
authors.initials: KN
authors.lastname: Alagramam
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D016057:Evoked Potentials, Auditory, Brain Stem; D005838:Genotype; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human