Null mutation of alpha1D Ca2+ channel gene results in deafness but no vestibular defect in mice

J Assoc Res Otolaryngol. 2004 Jun;5(2):215-26. doi: 10.1007/s10162-003-4020-3.


Multiple Ca2+ channels confer diverse functions to hair cells of the auditory and vestibular organs in the mammalian inner ear. We used gene-targeting technology to generate alpha1D Ca2+ channel-deficient mice to determine the physiological role of these Ca2+ channels in hearing and balance. Analyses of auditory-evoked brainstem recordings confirmed that alpha1D-/- mice were deaf and revealed that heterozygous (alpha1D+/-) mice have increased hearing thresholds. However, hearing deficits in alpha1D+/- mice were manifested mainly by the increase in threshold of low-frequency sounds. In contrast to impaired hearing, alpha1D-/- mice have balance performances equivalent to their wild-type littermates. Light and electron microscope analyses of the inner ear revealed outer hair cell loss at the apical cochlea, but no apparent abnormality at the basal cochlea and the vestibule. We determined the mechanisms underlying the auditory function defects and the normal vestibular functions by examining the Ba2+ currents in cochlear inner and outer hair cells versus utricular hair cells in alpha1D+/- mice. Whereas the whole-cell Ba2+ currents in inner hair cells consist mainly of the nimodipine-sensitive current (approximately 85%), the utricular hair cells express only approximately 50% of this channel subtype. Thus, differential expression of alpha1D channels in the cochlear and utricular hair cells confers the phenotype of the alpha1D null mutant mice. Because vestibular and cochlear hair cells share common features and null deletion of several genes have yielded both deafness and imbalance in mice, alpha1D null mutant mice may serve as a model to disentangle vestibular from auditory-specific functions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Auditory Threshold
  • Barium / metabolism
  • Calcium Channels, L-Type / genetics*
  • Cochlea / pathology
  • Cochlea / physiopathology
  • Deafness / genetics*
  • Deafness / pathology
  • Deafness / physiopathology*
  • Evoked Potentials, Auditory, Brain Stem
  • Hair Cells, Auditory, Outer / pathology
  • Hair Cells, Auditory, Outer / physiology*
  • Hair Cells, Auditory, Outer / ultrastructure
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Electron, Scanning
  • Patch-Clamp Techniques
  • Phenotype
  • Postural Balance / physiology
  • Saccule and Utricle / cytology
  • Saccule and Utricle / physiology
  • Vestibule, Labyrinth / physiology*


  • Cacna1d protein, mouse
  • Calcium Channels, L-Type
  • Barium