查看Ch15 Sensory Transduction的源代码

=== 内毛细胞转导声音，而外毛细胞的主动运动会放大信号 ===

<b style=color:#0ae>Inner hair cells transduce sound, whereas the active movements of outer hair cells amplify the signal</b>

The business end of the cochlea is the organ of Corti [N15-11], the portion of the basilar membrane that contains the hair cells. The organ of Corti stretches the length of the basilar membrane and has four rows of hair cells: one row of ~3500 inner hair cells and three rows with a total of ~16,000 outer hair cells (Fig. 15-22). In the auditory system, the arrangement of stereovilli is also quite orderly. The hair cells lie within a matrix of supporting cells, with their apical ends facing the endolymph of the scala media (Fig. 15-23A). The stereovilli of inner hair cells (see Fig. 15-23B) are unique in that they float freely in the endolymph. The stereovilli of the outer hair cells (see Fig. 15-23C) project into the gelatinous, collagen-containing tectorial membrane. The tectorial membrane is firmly attached only along one edge, with a sort of hinge, so that it is free to tilt up and down.

耳蜗的末端是 Corti 的器官 [N15-11]，是包含毛细胞的基底膜部分。Corti 器官延伸到基底膜的长度，有四排毛细胞：一排 ~3500 个内毛细胞，三排总共 ~16,000 个外毛细胞（图 15-22）。在听觉系统中，立体绒毛的排列也相当有序。毛细胞位于支持细胞基质中，其顶端面向中阶介质的内淋巴液（图 15-23A）。内毛细胞的立体绒毛（见图 15-23B）的独特之处在于它们在内淋巴中自由漂浮。外毛细胞的立体绒毛（见图 15-23C）投射到凝胶状、含有胶原蛋白的盖膜中。盖膜仅沿一个边缘牢固地连接，带有一种铰链，因此它可以自由地上下倾斜。


How do air pressure waves actually stimulate the auditory hair cells? Movements of the stapes against the oval window create traveling pressure waves within the cochlear fluids. Consider, for example, what happens as sound pressure falls in the outer ear.

气压波实际上是如何刺激听觉毛细胞的？镫骨对椭圆窗的运动会在耳蜗液内产生行进的压力波。例如，考虑一下当声压落在外耳中时会发生什么。


Step 1: Stapes moves outward. As a result, the oval window moves outward, causing pressure in the scala vestibuli to decrease. Because the perilymph that fills the scala vestibuli and scala tympani is incompressible and the cochlea is encased in rigid bone, the round window moves inward (see Fig. 15-19B).

第 1 步：镫骨向外移动。结果，椭圆形窗口向外移动，导致前庭鳞片中的压力降低。因为填充前庭鳞和鼓膜的外淋巴是不可压缩的，并且耳蜗被坚硬的骨包裹，所以圆窗向内移动（见图 15-19B）。

Step 2: Scala vestibuli pressure falls below scala tympani pressure.

第 2 步：前庭阶压力低于鼓膜间隙压力。

Step 3: Basilar membrane bows upward. Because Reissner’s membrane is very thin and flexible, the low scala vestibuli pressure pulls up the incompressible scala media, which in turn causes the basilar membrane (and the organ of Corti) to bow upward.

第 3 步：基底膜向上弯曲。因为前庭膜 (Reissner’s membrane) 非常薄且有弹性，低前庭标张压力会拉起不可压缩的标张介质，进而导致基底膜（和 Corti 器官）向上弯曲。


Step 4: Organ of Corti shears toward hinge of tectorial membrane. The upward bowing of the basilar membrane creates a shear force between the hair bundle of the outer hair cells and the attached tectorial membrane.

第 4 步：Corti 器官向盖膜铰链剪切。基底膜的向上弯曲在外毛细胞的发束和附着的盖膜之间产生剪切力。

Step 5: Hair bundles of outer hair cells tilt toward their longer stereovilli.

第 5 步：外毛细胞的发束向较长的立体绒毛倾斜。

Step 6: Transduction channels open in outer hair cells. Because K+ is the major ion, the result is depolarization of the outer hair cells (see Fig. 15-16A)—mechanical to electrical transduction. The transduction-induced changes in membrane potential are called receptor potentials. The molecular mechanisms of these Vm changes (see p. 373) are basically the same as in vestibular hair cells.

第 6 步：转导通道在外毛细胞中打开。因为 K+ 是主要离子，结果是外毛细胞去极化（见图 15-16A）——机械到电转导。转导诱导的膜电位变化称为受体电位。这些 Vm 变化的分子机制（见第 373 页）与前庭毛细胞基本相同。


Step 7: Depolarization contracts the motor protein prestin. Outer hair cells of mammals express very high levels of prestin (named for the musical notation presto, or fast). The contraction of myriad prestin molecules—each attached to its neighbors—causes the outer hair cell to contract; this phenomenon is unique to outer hair cells and is called electrical to mechanical transduction or electromotility. Conversely, hyperpolarization (during downward movements of the basilar membrane) causes outer hair cells to elongate. Indeed, imposing changes in Vm causes cell length to change by as much as ~5%. The change in shape is fast, beginning within 100 μs. The mechanical response of the outer hair cell does not depend on ATP, microtubule or actin systems, extracellular Ca2+, or changes in cell volume. Prestin is a member of the SLC26 family of anion transporters (see p. 125), although it is not clear whether prestin also functions as an anion transporter.

第 7 步：去极化收缩运动蛋白 prestin。哺乳动物的外毛细胞表达非常高水平的 prestin （以乐谱 presto 或 fast 命名）。无数 prestin 分子的收缩——每个分子都附着在它的邻居上——导致外毛细胞收缩;这种现象是外毛细胞独有的，称为电到机械转导或电动。相反，超极化（在基底膜向下运动期间）会导致外毛细胞伸长。事实上，施加 Vm 的变化会导致细胞长度变化多达 ~5%。形状的变化很快，从 100 μs 开始。外毛细胞的机械反应不依赖于 ATP、微管或肌动蛋白系统、细胞外 Ca2+ 或细胞体积的变化。Prestin 是阴离子转运蛋白 SLC26 家族的成员（参见第 125 页），尽管尚不清楚 Prestin 是否也作为阴离子转运蛋白发挥作用。


Step 8: Contraction of outer hair cells accentuates upward movement of the basilar membrane. Conversely, outer hair cell elongation (during downward movements of the basilar membrane) accentuates the downward movement of the basilar membrane. Thus, outer hair cells act as a cochlear amplifier—sensing and then rapidly accentuating movements of the basilar membrane. The electromotility of outer hair cells is a prerequisite for sensitive hearing and, as we will see (see pp. 380–383), the ability to discriminate frequencies sharply. In the absence of prestin, the cochlear amplifier ceases to function and animals become deaf.

第 8 步：外毛细胞的收缩加剧了基底膜的向上运动。相反，外毛细胞伸长（在基底膜向下运动期间）突出了基底膜的向下运动。因此，外毛细胞充当人工耳蜗放大器——感应并迅速强调基底膜的运动。外毛细胞的电动性是敏感听觉的先决条件，正如我们将看到的（参见第 380-383 页），能够敏锐地区分频率的能力。在没有 prestin 的情况下，人工耳蜗放大器停止工作，动物变得耳聋。

Step 9: Endolymph moves beneath the tectorial membrane. The upward movement of the basilar membrane— accentuated by the cochlear amplifier—forces endolymph to flow out from beneath the tectorial membrane, toward its tip.

第 9 步：内淋巴液移动到盖膜下方。基底膜的向上运动（由人工耳蜗放大器加强）迫使内淋巴液从盖膜下方流出，流向其尖端。


Step 10: Inner hair cell hair bundles bend toward longer stereovilli. The flow of endolymph now causes the freefloating hair bundles of the inner hair cells to bend.

第 10 步：内毛细胞毛束向较长的立体绒毛弯曲。内淋巴液的流动现在导致内毛细胞的自由漂浮的发束弯曲。

Step 11: Transduction channels open in inner hair cells. As in the outer hair cells, the result is a depolarization.

第 11 步：转导通道在内毛细胞中打开。与外层毛细胞一样，结果是去极化。

Step 12: Depolarization opens voltage-gated Ca2+ channels. [Ca2+]i rises in the inner hair cells.

第 12 步：去极化打开电压门控 Ca2+ 通道。[Ca2+]i 在内毛细胞中上升。

Step 13: Synaptic vesicles fuse, releasing glutamate. The neurotransmitter triggers action potentials in afferent neurons, relaying auditory signals to the brainstem. Note that the main response to depolarization is very different in the two types of hair cells. The outer hair cell contracts and thereby amplifies the movement of the basilar membrane. The inner hair cell releases neurotransmitter.

第 13 步：突触囊泡融合，释放谷氨酸。神经递质触发传入神经元的动作电位，将听觉信号传递到脑干。请注意，在两种类型的毛细胞中，对去极化的主要反应非常不同。外毛细胞收缩，从而放大基底膜的运动。内毛细胞释放神经递质。


When the stapes reverses direction and moves inward, all of these processes reverse as well. The basilar membrane bows downward. In the outer hair cells, transduction channels close, causing hyperpolarization and cell elongation. The accentuated downward movement of the basilar membrane causes endolymph to move back under the tectorial membrane. In inner hair cells, transduction channels close, causing hyperpolarization and reduced neurotransmitter release.

当镫骨反转方向并向内移动时，所有这些过程也会反转。基底膜向下弯曲。在外毛细胞中，转导通道关闭，导致超极化和细胞伸长。基底膜的强烈向下运动导致内淋巴液回到盖膜下。在内毛细胞中，转导通道关闭，导致超极化和神经递质释放减少。


A fascinating clue to the existence of the cochlear amplifier was the early observation that the ear not only detects sounds, but also generates them! Short click sounds trigger an “echo,” a brief vibration of the tympanic membrane that far outlasts the click. A microphone in the auditory canal can detect the echo, which is called an evoked otoacoustic emission. On occasion, damaged ears may produce spontaneous otoacoustic emissions that can even be loud enough to be heard by a nearby listener. N15-12 The source of evoked otoacoustic emissions is the prestin-mediated cochlear amplifier: sounds outside the ear lead to vibrations of the basilar membrane, which trigger active length changes of the outer hair cells, and these in turn accentuate the vibrations of the basilar membrane (step 8). In otoacoustic emission, the system then works in reverse as the basilar membrane causes pressure waves in the cochlear fluids, which vibrate the oval window, ossicles, and tympanic membrane, and finally generates new pressure waves in the air of the auditory canal.

人工耳蜗放大器存在的一个迷人线索是早期的观察，即耳朵不仅可以检测到声音，还可以产生声音！短促的咔嗒声会触发“回声”，即鼓膜的短暂振动，其持续时间远远超过咔嗒声。耳道中的麦克风可以检测到回声，这称为诱发耳声发射。有时，受损的耳朵可能会产生自发的耳声发射，甚至可能大到足以让附近的听众听到[N15-12]。诱发耳声发射的来源是 Prestin 介导的耳蜗放大器：耳外的声音导致基底膜的振动，从而触发外毛细胞的活动长度变化，这些变化反过来又加剧了基底膜的振动（步骤 8）。在耳声发射中，该系统随后反向工作，因为基底膜在耳蜗液中产生压力波，从而振动椭圆形窗口、听小骨和鼓膜，最后在耳道的空气中产生新的压力波。


The cochlea receives sensory and motor innervation from the auditory or cochlear nerve, a branch of CN VIII. We discuss the motor innervation below (see p. 382). The cell bodies of the sensory or afferent neurons of the cochlear nerve lie within the spiral ganglion, which corkscrews up around the axis of the cochlea (see Fig. 15-20, lower left). The dendrites of these neurons contact nearby hair cells, whereas the axons project to the cochlear nucleus in the brainstem (see Fig. 16-15). About 95% of the roughly 30,000 sensory neurons (i.e., type I cells) of each cochlear nerve innervate the relatively few inner hair cells—the true auditory sensory cells. The remaining 5% of spiral ganglion neurons (i.e., type II cells) innervate the abundant outer hair cells, which are so poorly innervated that they must contribute very little direct information about sound to the brain.

耳蜗接收来自听觉或耳蜗神经（CN VIII 的一个分支）的感觉和运动神经支配。我们在下面讨论运动神经支配（见第 382 页）。耳蜗神经的感觉或传入神经元的细胞体位于螺旋神经节内，螺旋神经节围绕耳蜗轴线螺旋状（见图 15-20，左下角）。这些神经元的树突接触附近的毛细胞，而轴突投射到脑干中的耳蜗核（见图 16-15）。每个耳蜗神经的大约 30,000 个感觉神经元（即 I 型细胞）中约有 95% 支配相对较少的内毛细胞——真正的听觉感觉细胞。其余 5% 的螺旋神经节神经元（即 II 型细胞）支配丰富的外毛细胞，这些细胞的神经支配非常差，以至于它们必须向大脑提供很少的声音直接信息。

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