L-type voltage-gated calcium channel is involved in the pathogenesis of acoustic injury in the cochlea.
Excessive calcium entry into cells leads to cell death, and voltage-gated calcium channels (VGCCs) are responsible for the calcium entry in the central nervous system. VGCC blockers inhibit excessive calcium entry and protect the central nervous system against various types of injury. The purpose of the present study was to identify the type of calcium channels that is responsible for acoustic injury of the cochlea. The effects of L- and T-type VGCC blockers on acoustic injury were examined. Female ddY mice, at 8 weeks of age, were used in this study. The animals were subjected to a 4-kHz pure tone of 128-dB sound pressure level (SPL) for 4 hours through an open field system inside a sound-exposure box. A L-type or T-type VGCC blocker was administered immediately before acoustic overexposure. The hearing ability was evaluated using the auditory brainstem response (ABR). ABR is an electrical signal evoked from the brainstem by the sound. After the final ABR measurement at two weeks after acoustic overexposure, cell nuclei in the organ of Corti were stained with propidium iodide, and hair cell loss was calculated in a region 3.66 mm from the apex. Each of four L-type VGCC blockers tested, i.e. diltiazem, verapamil, nicardipine and nimodipine, significantly improved shifts of the ABR threshold from the pre-exposure levels. In addition, each L-type VGCC blocker consistently decreased hair cell loss, but not a given T-type calcium blocker. The present findings suggest that the L-type VGCC is involved in the pathogenesis of acoustic injury in the cochlea.
Uemaetomari
Isao
I
Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Tabuchi
Keiji
K
Nakamagoe
Mariko
M
Tanaka
Syuho
S
Murashita
Hidekazu
H
Hara
Akira
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003051:Cochlea / Q000473:pathology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism / Q000473:pathology; D051379:Mice
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type