Bobbin Richard P, Salt Alec N
Kresge Hearing Research Laboratory, Department of Otolaryngology, Louisiana State University School of Medicine, New Orleans, LA 70112-2234, USA.
Hear Res. 2005 Jul;205(1-2):35-43. doi: 10.1016/j.heares.2005.02.009.
ATP receptor agonists and antagonists alter cochlear mechanics as measured by changes in distortion product otoacoustic emissions (DPOAE). Some of the effects on DPOAEs are consistent with the hypothesis that ATP affects mechano-electrical transduction and the operating point of the outer hair cells (OHCs). This hypothesis was tested by monitoring the effect of ATP-gamma-S on the operating point of the OHCs. Guinea pigs anesthetized with urethane and with sectioned middle ear muscles were used. The cochlear microphonic (CM) was recorded differentially (scala vestibuli referenced to scala tympani) across the basal turn before and after perfusion (20 min) of the perilymph compartment with artificial perilymph (AP) and ATP-gamma-S dissolved in AP. The operating point was derived from the cochlear microphonics (CM) recorded in response low frequency (200 Hz) tones at high level (106, 112 and 118 dB SPL). The analysis procedure used a Boltzmann function to simulate the CM waveform and the Boltzmann parameters were adjusted to best-fit the calculated waveform to the CM. Compared to the initial perfusion with AP, ATP-gamma-S (333 microM) enhanced peak clipping of the positive peak of the CM (that occurs during organ of Corti displacements towards scala tympani), which was in keeping with ATP-induced displacement of the transducer towards scala tympani. CM waveform analysis quantified the degree of displacement and showed that the changes were consistent with the stimulus being centered on a different region of the transducer curve. The change of operating point meant that the stimulus was applied to a region of the transducer curve where there was greater saturation of the output on excursions towards scala tympani and less saturation towards scala vestibuli. A significant degree of recovery of the operating point was observed after washing with AP. Dose response curves generated by perfusing ATP-gamma-S (333 microM) in a cumulative manner yielded an EC(50) of 19.8 microM. The ATP antagonist PPADS (0.1 mM) failed to block the effect of ATP-gamma-S on operating point, suggesting the response was due to activation of metabotropic and not ionotropic ATP receptors. Multiple perfusions of AP had no significant effect (118 and 112 dB) or moved the operating point slightly (106 dB) in the direction opposite of ATP-gamma-S. Results are consistent with an ATP-gamma-S induced transducer change comparable to a static movement of the organ of Corti or reticular lamina towards scala tympani.
ATP受体激动剂和拮抗剂可改变耳蜗力学，这通过畸变产物耳声发射（DPOAE）的变化来衡量。对DPOAE的一些影响与ATP影响机械电转导和外毛细胞（OHC）工作点的假说一致。通过监测ATP-γ-S对OHC工作点的影响来检验这一假说。使用用氨基甲酸乙酯麻醉并切断中耳肌肉的豚鼠。在使用人工外淋巴（AP）和溶解在AP中的ATP-γ-S灌注（20分钟）外淋巴腔前后，在基底转以差分方式记录耳蜗微音电位（CM）（前庭阶相对于鼓阶）。工作点源自对高频（200 Hz）、高强度（106、112和118 dB SPL）纯音响应记录的耳蜗微音电位（CM）。分析程序使用玻尔兹曼函数模拟CM波形，并调整玻尔兹曼参数以使计算出的波形与CM最佳拟合。与最初用AP灌注相比，ATP-γ-S（333 μM）增强了CM正峰的峰值削波（在柯蒂氏器向鼓阶位移期间出现），这与ATP诱导的换能器向鼓阶位移一致。CM波形分析量化了位移程度，并表明这些变化与刺激集中在换能器曲线的不同区域一致。工作点的变化意味着刺激施加于换能器曲线的一个区域，在该区域向鼓阶偏移时输出有更大饱和度，而向前庭阶偏移时饱和度较小。用AP冲洗后观察到工作点有显著程度的恢复。以累积方式灌注ATP-γ-S（333 μM）产生的剂量反应曲线得出的EC(50)为19.8 μM。ATP拮抗剂PPADS（0.1 mM）未能阻断ATP-γ-S对工作点的影响，表明该反应是由于代谢型而非离子型ATP受体的激活。多次灌注AP没有显著影响（118和112 dB），或者在与ATP-γ-S相反的方向上使工作点略有移动（106 dB）。结果与ATP-γ-S诱导的换能器变化一致，该变化类似于柯蒂氏器或网状板向鼓阶的静态移动。
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