Batta Tamás József, Panyi György, Szucs Attila, Sziklai István
ORL Clinic, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, H-4012 Hungary.
Eur J Neurosci. 2004 Dec;20(12):3364-70. doi: 10.1111/j.1460-9568.2004.03797.x.
Acetylcholine (ACh) and GABA, the main neurotransmitters of the efferent innervation of the outer hair cells (OHCs), are assumed to regulate the efficacy of the cochlear amplifier through a variety of mechanisms. The recently described stretch-induced changes of the lateral wall stiffness (regulatory stiffness response) and the stretch-induced slow cell motility of OHCs may be important regulatory mechanisms in this process. We found that ACh in cochleobasal OHCs significantly reduces the stiffness of the lateral wall but increases the regulatory stiffness response and stretch-induced slow cell motility. Qualitatively similar cellular responses were evoked by GABA in cochleoapical OHCs. The effects of ACh could be inhibited by strychnine, the specific inhibitor of the alpha(9) ACh receptors expressed in OHCs, whereas the effects of GABA could be blocked by bicuculline, a specific GABA(A) receptor antagonist. In the absence of extracellular Ca(2+) the effects of ACh and GABA on the regulatory stiffness response were reduced, indicating the involvement of Ca(2+) in the control of this process. Based on our results we suggest that efferent innervation protects the organ of Corti against high sound intensities and supports adaptation by modification of the micromechanical properties of OHCs. This could be governed by ACh and GABA indirectly, via the potentiation of stretch-induced cell shortening in a Ca(2+)-dependent manner, rather than by a direct stiffness regulation-related mechanism.
乙酰胆碱（ACh）和γ-氨基丁酸（GABA）是外毛细胞（OHC）传出神经支配的主要神经递质，被认为通过多种机制调节耳蜗放大器的效能。最近描述的侧壁刚度拉伸诱导变化（调节刚度反应）和OHC的拉伸诱导慢细胞运动可能是这一过程中的重要调节机制。我们发现，耳蜗基部OHC中的ACh显著降低了侧壁的刚度，但增加了调节刚度反应和拉伸诱导慢细胞运动。耳蜗顶部OHC中的GABA诱发了定性相似的细胞反应。ACh的作用可被士的宁抑制，士的宁是OHC中表达的α(9) ACh受体的特异性抑制剂，而GABA的作用可被荷包牡丹碱阻断，荷包牡丹碱是一种特异性GABA(A)受体拮抗剂。在没有细胞外Ca(2+)的情况下，ACh和GABA对调节刚度反应的作用减弱，表明Ca(2+)参与了这一过程的控制。基于我们的结果，我们认为传出神经支配可保护柯蒂氏器免受高声强影响，并通过改变OHC的微机械特性来支持适应性。这可能是由ACh和GABA间接控制的，通过以Ca(2+)依赖的方式增强拉伸诱导的细胞缩短，而不是通过直接的刚度调节相关机制。
