Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blocker

Yu,Ya‑Feng; Wu,Wen‑Ying; Xiao,Gen‑Sheng; Ling,Hong‑Yang; Pan,Chen

doi:10.3892/etm.2016.2970

Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blocker

Authors:
- Ya‑Feng Yu
- Wen‑Ying Wu
- Gen‑Sheng Xiao
- Hong‑Yang Ling
- Chen Pan
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Affiliations: Department of Otolaryngology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: January 8, 2016 https://doi.org/10.3892/etm.2016.2970
Pages: 1039-1044

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Abstract

The aim of the present study was to investigate the protective effect of T-type calcium channel blockers against presbycusis, using a C57BL/6J mice model. The expression of three T‑type calcium channel receptor subunits in the cochlea of 6‑8‑week‑old C57BL/6J mice was evaluated using reverse transcription‑quantitative polymerase chain reaction. The results confirmed that the three subunits were expressed in the cochlea. In addition, the capacity of T‑type calcium channel blockers to protect the cochlear hair cells of 24‑26‑week‑old C57BL/6J mice was investigated in mice treated with mibefradil, benidipine or saline for 4 weeks. Differences in hearing threshold were detected using auditory brainstem recording (ABR), while differences in amplitudes were measured using a distortion product otoacoustic emission (DPOAE) test. The ABR test results showed that the hearing threshold significantly decreased at 24 kHz in the mibefradil‑treated and benidipine‑treated groups compared with the saline‑treated group. The DPOAE amplitudes in the mibefradil‑treated group were increased compared with those in the saline‑treated group at the F2 frequencies of 11.3 and 13.4 kHz. Furthermore, the DPOAE amplitudes in the benidipine‑treated group were increased compared with those in the saline‑treated group at an F2 frequency of 13.4 kHz. The loss of outer hair cells (OHCs) was not evident in the mibefradil‑treated group; however, the stereocilia of the inner hair cells (IHCs) were disorganised and sparse. In summary, these results indicate that the administration of a T‑type calcium channel blocker for four consecutive weeks may improve the hearing at 24 kHz of 24‑26‑week‑old C57BL/6J mice. The function and morphology of the OHCs of the C57BL/6J mice were significantly altered by the administration of a T‑type calcium channel blocker; however, the IHCs were unaffected.

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1	Corso JF: Auditory processes and aging: Significant problems for research. Exp Aging Res. 10:171–174. 1984. View Article : Google Scholar : PubMed/NCBI
2	Olshansky SJ, Carnes BA and Cassel CK: The aging of the human species. Sci Am. 268:46–52. 1993. View Article : Google Scholar : PubMed/NCBI
3	Gates GA and Mills JH: Presbycusis. Lancet. 366:1111–1120. 2005. View Article : Google Scholar : PubMed/NCBI
4	Johnsson LG and Hawkins JE Jr: Sensory and neural degeneration with aging, as seen in microdissections of the human inner ear. Ann Otol Rhinol Laryngol. 81:179–193. 1972. View Article : Google Scholar : PubMed/NCBI
5	Schuknecht HF and Gacek MR: Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol. 102:1–16. 1993.PubMed/NCBI
6	Willott JF, Parham K and Hunter KP: Comparison of the auditory sensitivity of neurons in the cochlear nucleus and inferior colliculus of young and aging C57BL/6J and CBA/J mice. Hear Res. 53:78–94. 1991. View Article : Google Scholar : PubMed/NCBI
7	Pickles JO: Mutation in mitochondrial DNA as a cause of presbyacusis. Audiol Neurootol. 9:23–33. 2004. View Article : Google Scholar : PubMed/NCBI
8	Trump BF and Berezesky IK: The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis. Curr Opin Cell Biol. 4:227–232. 1992. View Article : Google Scholar : PubMed/NCBI
9	Orrenius S, McCabe MJ Jr and Nicotera P: Ca(2+)-dependent mechanisms of cytotoxicity and programmed cell death. Toxicol Lett 64–65 Spec No: 357–364. 1992. View Article : Google Scholar
10	Fridberger A, Flock A, Ulfendahl M and Flock B: Acoustic overstimulation increases outer hair cell Ca2+ concentrations and causes dynamic contractions of the hearing organ. Proc Natl Acad Sci USA. 95:7127–7132. 1998. View Article : Google Scholar : PubMed/NCBI
11	Li H, Liu H and Heller S: Pluripotent stem cells from the adult mouse inner ear. Nat Med. 9:1293–1299. 2003. View Article : Google Scholar : PubMed/NCBI
12	Levic S and Dulon D: The temporal characteristics of Ca2+ entry through L-type and T-type Ca2+ channels shape exocytosis efficiency in chick auditory hair cells during development. J Neurophysiol. 108:3116–3123. 2012. View Article : Google Scholar : PubMed/NCBI
13	Hafidi A and Dulon D: Developmental expression of Ca(v)1.3 (alpha1d) calcium channels in the mouse inner ear. Brain Res Dev Brain Res. 150:167–175. 2004. View Article : Google Scholar : PubMed/NCBI
14	Shen H, Zhang B, Shin JH, Lei D, Du Y, Gao X, Wang Q, Ohlemiller KK, Piccirillo J and Bao J: Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hear Res. 226:52–60. 2007. View Article : Google Scholar : PubMed/NCBI
15	Willott JF: Aging and the Auditory System: Anatomy, Physiology, and Psychophysics. San Diego, CA: Singular Publishing Group, Inc. 1–295. 1991.
16	Johnson KR, Erway LC, Cook SA, Willott JF and Zheng QY: A major gene affecting age-related hearing loss in C57BL/6J mice. Hear Res. 114:83–92. 1997. View Article : Google Scholar : PubMed/NCBI
17	Yu YF, Zhai F, Dai CF and Hu JJ: The relationship between age-related hearing loss and synaptic changes in the hippocampus of C57BL/6J mice. Exp Gerontol. 46:716–722. 2011. View Article : Google Scholar : PubMed/NCBI
18	Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, et al: Mitochondrial DNA mutations, oxidative stress and apoptosis in mammalian aging. Science. 309:481–484. 2005. View Article : Google Scholar : PubMed/NCBI
19	Wu Z, Zhang J and Zhao B: Superoxide anion regulates the mitochondrial free Ca2+ through uncoupling proteins. Antioxid Redox Signal. 11:1805–1818. 2009. View Article : Google Scholar : PubMed/NCBI
20	Giacomello M, De Mario A, Primerano S, Brini M and Carafoli E: Hair cells, plasma membrane Ca²⁺ ATPase and deafness. Int J Biochem Cell Biol. 44:679–683. 2012. View Article : Google Scholar : PubMed/NCBI
21	Karlstad J, Sun Y and Singh BB: Ca(2+) signaling: An outlook on the characterization of ca(2+) channels and their importance in cellular functions. Adv Exp Med Biol. 740:143–157. 2012. View Article : Google Scholar : PubMed/NCBI
22	Eatock RA and Hurley KM: Functional development of hair cells. Curr Top Dev Biol. 57:389–448. 2003. View Article : Google Scholar : PubMed/NCBI
23	Spitzer NC: Activity-dependent neuronal differentiation prior to synapse formation: The functions of calcium transients. J Physiol Paris. 96:73–80. 2002. View Article : Google Scholar : PubMed/NCBI
24	Triggle DJ: The pharmacology of ion channels: With particular reference to voltage-gated Ca2+ channels. Eur J Pharmacol. 375:311–325. 1999. View Article : Google Scholar : PubMed/NCBI
25	Liu J, Niu YG, Li WX, Yuan YY, Han WJ, Yu N, Yang SM and Li XQ: Interaction of a calcium channel blocker with noise in cochlear function in guinea pig. Acta Otolaryngol. 132:1140–1144. 2012. View Article : Google Scholar : PubMed/NCBI
26	Kansu L, Ozkarakas H, Efendi H and Okar I: Protective effects of pentoxifylline and nimodipine on acoustic trauma in Guinea pig cochlea. Otol Neurotol. 32:919–925. 2011. View Article : Google Scholar : PubMed/NCBI
27	Inagaki A, Ugawa S, Yamamura H, Murakami S and Shimada S: The CaV3.1 T-type Ca2+ channel contributes to voltage-dependent calcium currents in rat outer hair cells. Brain Res. 1201:68–77. 2008. View Article : Google Scholar : PubMed/NCBI
28	Sandmann S, Spitznagel H, Chung O, Xia QG, Illner S, Jänichen G, Rossius B, Daemen MJ and Unger T: Effects of the calcium channel antagonist mibefradil on haemodynamic and morphological parameters in myocardial infarction-induced cardiac failure in rats. Cardiovasc Res. 39:339–350. 1998. View Article : Google Scholar : PubMed/NCBI
29	Yao K, Nagashima K and Miki H: Pharmacological, pharmacokinetic and clinical properties of benidipine hydrochloride, a novel, long-acting calcium channel blocker. J Pharmacol Sci. 100:243–261. 2006. View Article : Google Scholar : PubMed/NCBI
30	Kemp DT: Otoacoustic emissions, their origin in cochlear function and use. Br Med Bull. 63:223–241. 2002. View Article : Google Scholar : PubMed/NCBI
31	Spongr VP, Flood DG, Frisina RD and Salvi RJ: Quantitative measures of hair cell loss in CBA and C57BL/6 mice throughout their life spans. J Acoust Soc Am. 101:3546–3553. 1997. View Article : Google Scholar : PubMed/NCBI