Department of Physiology and Biophysics.
Neuroscience Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
J Neurosci. 2019 Nov 13;39(46):9098-9106. doi: 10.1523/JNEUROSCI.1408-19.2019. Epub 2019 Oct 2.
Sound detection in auditory sensory hair cells depends on the deflection of the stereocilia hair bundle which opens mechano-electric transduction (MET) channels. Adaptation is hypothesized to be a critical property of MET that contributes to the auditory system's wide dynamic range and sharp frequency selectivity. Our recent work using a stiff probe to displace hair bundles showed that the fastest adaptation mechanism (fast adaptation) does not require calcium entry. Using fluid-jet stimuli, others obtained data showing only a calcium-dependent fast adaptation response. Because cochlear stereocilia do not move coherently and the hair cell response depends critically on the magnitude and time course of the hair bundle deflection, we developed a high-speed imaging technique to quantify this deflection in rat cochlear hair cells. The fluid jet delivers a force stimulus, and force steps lead to a complex time course of hair bundle displacement (mechanical creep), which affects the hair cell's macroscopic MET current response by masking the time course of the fast adaptation response. Modifying the fluid-jet stimulus to generate a hair bundle displacement step produced rapidly adapting currents that did not depend on membrane potential, confirming that fast adaptation does not depend on calcium entry. MET current responses differ with stimulus modality and will shape receptor potentials of different hair cell types based on their stimulus mode. These transformations will directly affect how stimuli are encoded. Mechanotransduction by sensory hair cells represents a key first step for the sound sensing ability in vertebrates. The sharp frequency tuning and wide dynamic range of sound sensation are hypothesized to require a mechanotransduction adaptation mechanism. Recent work indicated that the apparent calcium dependence of the fastest adaptation differs with the method of cochlear hair cell stimulation. Here, we reconcile existing data and show that calcium entry does not drive the fastest adaptation process, independent of the stimulation method. With force stimulation of the hair bundle, adaptation manifests differently than with displacement stimulation, indicating that the stimulation mode of the hair bundle will affect the hair cell receptor current and stimulus coding.
声音在听觉感觉毛细胞中的检测依赖于纤毛束的偏斜，而纤毛束的偏斜则开启机械电转换（MET）通道。适应被假设为 MET 的一个关键特性，有助于听觉系统的宽动态范围和尖锐的频率选择性。我们最近使用刚性探针来移动毛束的工作表明，最快的适应机制（快速适应）不需要钙进入。使用流体喷射刺激，其他人获得的数据显示只有钙依赖性的快速适应反应。由于耳蜗纤毛不会一致地移动，并且毛细胞的反应取决于毛束偏斜的幅度和时间过程，我们开发了一种高速成像技术来量化大鼠耳蜗毛细胞中的这种偏斜。流体射流施加力刺激，力阶导致毛束位移的复杂时间过程（机械蠕变），通过掩盖快速适应反应的时间过程，影响毛细胞的宏观 MET 电流反应。修改流体喷射刺激以产生毛束位移阶跃会产生不依赖于膜电位的快速适应电流，证实快速适应不依赖于钙进入。MET 电流反应因刺激方式而异，根据其刺激模式，将塑造不同毛细胞类型的受体电位。这些转换将直接影响刺激的编码方式。感觉毛细胞的机械转导代表了脊椎动物声音感知能力的关键第一步。尖锐的频率调谐和宽的动态范围被假设需要机械转导适应机制。最近的工作表明，最快适应的表观钙依赖性因耳蜗毛细胞刺激的方法而异。在这里，我们调和现有的数据，并表明钙进入不会驱动最快的适应过程，而与刺激方法无关。通过毛束的力刺激，适应的表现与位移刺激不同，这表明毛束的刺激模式将影响毛细胞受体电流和刺激编码。
