Prevention and treatment of noise-induced hearing loss and cochlear synapse degeneration by potassium channel blockersin vivo

Author:

Zhao Hong-BoORCID,Liu Li-Man,Mei Ling,Quinonez Auraemil T,Roberts Rafael A,Lu Xiaoling

Abstract

AbstractNoise can induce hearing loss. In particularly, noise can induce cochlear synapse degeneration leading to hidden hearing loss, which is the most common type of hearing disorders in the clinic. Currently, there is no pharmacological treatment, particularly, no post-exposure (i.e., therapeutic) treatment available in the clinic. Here, we report that systematic administration of K+channel blockers before or after noise exposure could significantly attenuate NIHL and synapse degeneration. After systematic administration of a general K-channel blocker tetraethylammonium (TEA), the elevation of auditory brainstem response (ABR) thresholds after noise-exposure significantly reduced, and the active cochlear mechanics significantly improved. The therapeutic effect was further improved as the post-exposure administration time extending to 3 days. BK channel is a predominant K+channel in the inner hair cells. Systematic administration of a BK channel blocker GAL-021 after noise exposure also ameliorated hearing loss and improved hearing behavioral responses tested by acoustic startle response (ASR). Finally, both TEA and GAL-021 significantly attenuated noise-induced ribbon synapse degeneration. These data demonstrate that K+-channel blockers can prevent and treat NIHL and cochlear synapse degeneration. Our finding may aid in developing therapeutic strategies for post-exposure treatment of NIHL and synapse degeneration.Significance StatementNoise is a common deafness factor affecting more 100 million people in the United States. So far, there is no pharmacological treatment available. We show here that administration of K+channel blockers after noise exposure could attenuate noise-induced hearing loss and synapse degeneration, and improved behavioral responses. This is the first time to real the K+channel blockers that could treat noise-induced hearing loss and cochlear synaptopathy after noise exposure.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3