Localisation of the mechanotransducer channels in mammalian cochlear hair cells provides clues to their gating

Abstract

Our sense of hearing and balance relies on the very rapid gating of mechanotransducer channels known to be located close to the tops of the hair cell stereocilia within the stereociliary bundle. The molecular identity of the channels is unknown but functional aspects such as permeation, block and sensitivity to bundle displacement are well known. The channel has high calcium permeability and this feature has been used in conjunction with fast confocal calcium imaging to unambiguously localise the channels at the top of the two shorter rows of stereocilia in mammalian cochlear hair cells. The data suggest that they are completely absent from the tallest row. It is thought that the structures connecting stereocilia in adjacent rows, the tip links, are either directly responsible for the channel's mechanical gating, or are closely associated with the gating process. The channels must therefore be associated with the bottom part of the tip links and not the top. This feature has important implications for both the channel's gating mechanism and its regulatory adaptation mechanism. The tip link remains an attractive candidate for mechanical coupling between the bundle and the channel or an accessory protein. The localisation of the mechanotransducer channels to the lower end of the tip link represents an important milestone in the journey towards eventual identification of the channel and its gating mechanism.