Ca v 3.2 T-Type Calcium Channels Are Physiologically Mandatory for the Auditory System

Neuroscience. 2019 Jun 15;409:81-100. doi: 10.1016/j.neuroscience.2019.04.024. Epub 2019 Apr 25.

Abstract

Voltage-gated Ca2+ channels (VGCCs) play key roles in auditory perception and information processing within the inner ear and brainstem. Pharmacological inhibition of low voltage-activated (LVA) T-type Ca2+ channels is related to both age- and noise induced hearing loss in experimental animals and may represent a promising approach to the treatment of auditory impairment of various etiologies. Within the LVA Ca2+ channel subgroup, Cav3.2 is the most prominently expressed T-type channel entity in the cochlea and auditory brainstem. Thus, we performed a complete gender specific click and tone burst based auditory brainstem response (ABR) analysis of Cav3.2+/- and Cav3.2-/- mice, including i.a. temporal progression in hearing loss, amplitude growth function and wave latency analysis as well as a cochlear qPCR based evaluation of other VGCCs transcripts. Our results, based on a self-programmed automated wavelet approach, demonstrate that both heterozygous and Cav3.2 null mutant mice exhibit age-dependent increases in hearing thresholds at 5 months of age. In addition, complex alterations in WI-IV amplitudes and latencies were detected that were not attributable to alterations in the expression of other VGCCs in the auditory tract. Our results clearly demonstrate the important physiological role of Cav3.2 VGCCs in the spatiotemporal organization of auditory processing in young adult mice and suggest potential pharmacological targets for interventions in the future.

Keywords: T-type; auditory brainstem response; calcium channel; hair cells; sensorineural hearing loss; spiral ganglion neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Threshold / physiology*
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / metabolism*
  • Cochlea / metabolism
  • Hearing / physiology*
  • Hearing Loss / genetics
  • Hearing Loss / metabolism*
  • Mice
  • Mice, Knockout

Substances

  • Cacna1h protein, mouse
  • Calcium Channels, T-Type