Conductance properties of the α9α10 nicotinic acetylcholine receptor of neonatal mouse inner and outer hair cells

IF 2.5 2区 医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY Hearing Research Pub Date : 2024-10-01 DOI:10.1016/j.heares.2024.109126
Helen J Kennedy , Michael G Evans
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Abstract

In the developing cochlea, just before the onset of hearing on postnatal day 12, the medial olivocochlear efferent axons in synaptic contact with the inner hair cells (IHCs) start withdrawing and new efferent synaptic connections are formed on the outer hair cells (OHCs), thereby progressing towards the adult pattern of medial olivocochlear efferent innervation. The synapses are inhibitory, calcium influx through the α9α10 nicotinic acetylcholine receptors (nAChRs) driving opening of calcium-dependent potassium channels. The nAChRs appear to function similarly in IHCs and OHCs, although with probable kinetic differences. Our aim was to assess their functional similarity in the neonatal mouse cochlea by making whole-cell recordings from both hair cell types between postnatal day 7 and 10 when nAChRs are expressed. ACh was applied to voltage-clamped hair cells by pressure-ejection from a pipette. The cells were dialysed with a Cs+-based solution designed to eliminate calcium-dependent potassium currents. There were differences in amplitude, voltage-sensitivity and reversal potential of the nAChR currents between IHCs and OHCs. There was also some indication that IHC nAChRs have slower activation and desensitization kinetics, although the relatively slow ACh application limited interpretation of this result. These differences, particularly concerning the reversal potential, might indicate the presence of different auxiliary protein subunits of the α9α10 receptor in neonatal IHCs and OHCs.
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新生小鼠内外毛细胞α9α10烟碱乙酰胆碱受体的传导特性
在发育中的耳蜗中,就在出生后第 12 天开始出现听力之前,与内毛细胞(IHC)有突触接触的内侧橄榄耳传出轴突开始撤出,并在外毛细胞(OHC)上形成新的传出突触连接,从而向内侧橄榄耳传出神经支配的成人模式发展。突触是抑制性的,钙通过α9α10烟碱乙酰胆碱受体(nAChRs)流入,驱动钙依赖性钾通道开放。nAChRs在IHC和OHC中的功能似乎相似,但可能存在动力学差异。我们的目的是在新生小鼠耳蜗中对两种毛细胞类型进行全细胞记录,以评估它们在新生小鼠耳蜗中的功能相似性。通过移液管的压力喷射,向电压钳夹的毛细胞施加 ACh。用 Cs+ 基溶液透析细胞,以消除钙依赖性钾电流。IHC 和 OHC 之间的 nAChR 电流在振幅、电压敏感性和反向电位方面存在差异。还有一些迹象表明,IHC nAChRs 的激活和脱敏动力学较慢,尽管 ACh 的应用相对较慢限制了对这一结果的解释。这些差异,尤其是反转电位方面的差异,可能表明新生 IHC 和 OHC 中存在不同的 α9α10 受体辅助蛋白亚基。
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来源期刊
Hearing Research
Hearing Research 医学-耳鼻喉科学
CiteScore
5.30
自引率
14.30%
发文量
163
审稿时长
75 days
期刊介绍: The aim of the journal is to provide a forum for papers concerned with basic peripheral and central auditory mechanisms. Emphasis is on experimental and clinical studies, but theoretical and methodological papers will also be considered. The journal publishes original research papers, review and mini- review articles, rapid communications, method/protocol and perspective articles. Papers submitted should deal with auditory anatomy, physiology, psychophysics, imaging, modeling and behavioural studies in animals and humans, as well as hearing aids and cochlear implants. Papers dealing with the vestibular system are also considered for publication. Papers on comparative aspects of hearing and on effects of drugs and environmental contaminants on hearing function will also be considered. Clinical papers will be accepted when they contribute to the understanding of normal and pathological hearing functions.
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