Cav3.2 T-Type Calcium Channels Are Physiologically Mandatory for the Auditory System. (15th June 2019)

• Record Type: Journal Article
• Authors: Lundt, Andreas; Seidel, Robin; Soós, Julien; Henseler, Christina; Müller, Ralf; Bakki, Maheshwar; Arshaad, Muhammad Imran; Ehninger, Dan; Hescheler, Jürgen; Sachinidis, Agapios; Broich, Karl; Wormuth, Carola; Papazoglou, Anna; Weiergräber, Marco
• Is Part Of: Neuroscience. Volume 409(2019)
• Page Start: 81
• Page End: 100
• Publication Date: 2019-06-15
• Subjects: ABR auditory brainstem response -- AED antiepileptic drug -- AEP auditory evoked potential -- ARHL age-related hearing loss -- BERA brainstem evoked response audiometry -- BK big conductance Ca2+-activated K+ channel -- CWT continuous wavelet transform -- DHP dihydropyridine -- FFT Fast Fourier Transformation -- GT genotype -- HC hair cell -- HVA high voltage-activated -- IHC inner hair cell -- i.p. intraperitoneal -- IWI interwave-interval -- LL lateral leminiscus -- LSO lateral superior olive -- LVA low voltage-activated -- NIHL noise-induced hearing loss -- OHC outer hair cell -- (q)PCR quantitative polymerase chain reaction -- RT reverse transcription -- SD standard deviation -- SEM standard error of the mean -- SGN spiral ganglion neuron -- SK small conductance Ca2+-activated K+ channel -- SNR signal to noise ratio -- SOC superior olivary complex -- SPL sound pressure level -- SPON superior paraolivary nucleus -- TWs time windows -- VGCC voltage-gated Ca2+ channel; auditory brainstem response -- calcium channel -- hair cells -- spiral ganglion neuron -- T-type -- sensorineural hearing loss; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.04.024
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Voltage-gated Ca 2+ 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 Ca 2+ 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 Ca 2+ channel subgroup, Cav 3.2 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 Cav 3.2 +/- and Cav 3.2 -/- 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 Cav 3.2 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 Cav 3.2 VGCCs in the spatiotemporal organization of auditory processing in young adult mice and suggest potential pharmacological targets for interventions in the future. Highlights: Cav 3.2 +/- and Cav 3.2 -/- mice exhibit increased ABR thresholds upon click stimulation. Cav 3.2 +/- and Cav 3.2 -/- mice display altered tone burst evoked ABR thresholds. Cav 3.2 transgenic mice show altered amplitude growth function and wave latencies. Cav 3.2 calcium channels are mandatory for auditory information processing in adult mice.