Ch15 Sensory Transduction

2024年11月12日 (二) 17:04的版本

1 前庭和听觉转导：毛细胞

VESTIBULAR AND AUDITORY TRANSDUCTION: HAIR CELLS

Balancing on one foot and listening to music both involve sensory systems that have similar transduction mechanisms. Sensation in both the vestibular and auditory systems begins with the inner ear, and both use a highly specialized kind of receptor called the hair cell. Common structure and function often suggest a common origin, and indeed, the organs of mammalian hearing and balance both evolved from the lateral line organs present in all aquatic vertebrates. The lateral line consists of a series of pits or tubes along the flanks of an animal. Within each indentation are clusters of sensory cells that are similar to hair cells. These cells have microvilli-like structures that project into a gelatinous material that in turn is in contact with the water in which the animal swims. The lateral line is exquisitely sensitive to vibrations or pressure changes in the water in many animals, although it is also sensitive to temperature or electrical fields in some species. Reptiles abandoned the lateral line during their evolution, but they retained the hair cell– centered sensory structures of the inner ear that evolved from the lateral line.

单脚平衡和听音乐都涉及具有相似转导机制的感觉系统。前庭和听觉系统的感觉都从内耳开始，两者都使用一种称为毛细胞的高度专业化的受体。共同的结构和功能通常表明一个共同的起源，事实上，哺乳动物的听觉和平衡器官都是从所有水生脊椎动物中存在的侧线器官进化而来的。侧线由沿动物侧面的一系列凹坑或管子组成。每个凹痕内都有类似于毛细胞的感觉细胞簇。这些细胞具有微绒毛状结构，这些结构投射到凝胶状材料中，而凝胶状材料又与动物游泳的水接触。在许多动物中，侧线对水中的振动或压力变化非常敏感，尽管在某些物种中它也对温度或电场敏感。爬行动物在进化过程中放弃了侧线，但它们保留了从侧线进化而来的以毛细胞为中心的内耳感觉结构。

The vestibular system generates our sense of balance and the auditory system provides our sense of hearing. Vestibular sensation operates constantly while we are awake and communicates to the brain the head’s orientation and changes in the head’s motion. Such information is essential for generating muscle contractions that will put our body where we want it to be, reorienting the body when something pushes us aside (vestibulospinal reflexes), and moving our eyes continually so that the visual world stays fixed on our retinas even though our head may be nodding about (vestibuloocular reflexes). N15-4 Vestibular dysfunction can make it impossible to stabilize an image on our moving retinas, and it causes the disconcerting feeling that the world is uncontrollably moving around—vertigo. Walking and standing can be difficult or impossible. With time, compensatory adjustments are made as the brain learns to substitute more visual and proprioceptive cues to help guide smooth and accurate movements.

前庭系统产生我们的平衡感，听觉系统提供我们的听觉。当我们清醒时，前庭感觉不断运作，并将头部的方向和头部运动的变化传达给大脑。这些信息对于产生肌肉收缩至关重要，这将使我们的身体处于我们想要的位置，当有东西将我们推到一边时重新定位身体（前庭脊髓反射），以及不断移动我们的眼睛，以便视觉世界保持在我们的视网膜上，即使我们的头可能在点头（前庭脑膜反射）。N15-4 前庭功能障碍会导致我们无法稳定我们移动的视网膜上的图像，并导致世界不受控制地移动的令人不安的感觉——眩晕。行走和站立可能很困难或不可能。随着时间的推移，随着大脑学会用更多的视觉和本体感觉线索来代替，以帮助指导平稳和准确的运动，就会进行代偿性调整。

Auditory sensation is often at the forefront of our conscious experience, unlike vestibular information, which we rarely notice unless something goes wrong. Hearing is an exceptionally versatile process that allows us to detect things in our environment, to precisely identify their nature, to localize them well at a distance, and, through language, to communicate with speed, complexity, nuance, and emotion.

听觉感觉通常处于我们意识体验的最前沿，这与前庭信息不同，除非出现问题，否则我们很少注意到它。听觉是一个非常通用的过程，它使我们能够检测环境中的事物，精确识别它们的性质，在远处很好地定位它们，并通过语言以速度、复杂性、细微差别和情感进行交流。

1.1 沿一个轴弯曲毛细胞的立体绒毛会导致阳离子通道打开或关闭

Bending the stereovilli of hair cells along one axis causes cation channels to open or to close

Hair cells are mechanoreceptors that are specialized to detect minuscule movement along one particular axis. The hair cell is an epithelial cell (see pp. 43–45); the hair bundles project from the apical end, whereas synaptic contacts occur at the basal end. Hair cells are somewhat different in the vestibular and auditory systems. In this section, we illustrate concepts mainly with the vestibular hair cell (Fig. 15-15A), which comes in two subtypes. Vestibular type I cells have a bulbous basal area, surrounded by a calyx-shaped afferent nerve terminal (see Fig. 15-15B, left). Vestibular type II hair cells are more cylindrical and have several simple, boutonshaped afferent nerve terminals (see Fig. 15-15B, right). Auditory hair cells also come in two varieties, inner hair cells and outer hair cells (see pp. 378–380). However, all hair cells sense movement in basically the same way.

毛细胞是专门用于检测沿一个特定轴的微小运动的机械感受器。毛细胞是上皮细胞（见第 43-45 页）;发束从顶端伸出，而突触接触发生在基底端。前庭和听觉系统中的毛细胞略有不同。在本节中，我们主要用前庭毛细胞（图 15-15A）来说明概念，它有两种亚型。前庭 I 型细胞具有球状基部区域，周围环绕着花萼状传入神经末梢（见图 15-15B，左）。前庭 II 型毛细胞更圆柱形，有几个简单的钮扣形传入神经末梢（见图 15-15B，右）。听觉毛细胞也有两种类型，内毛细胞和外毛细胞（见第 378-380 页）。然而，所有毛细胞都以基本相同的方式感知运动。

As part of their hair bundles, vestibular hair cells (see Fig. 15-15B) have one large kinocilium, which is a true cilium with the characteristic 9 + 2 pattern of microtubules (see Fig. 2-11C). The role of the kinocilium is unknown. In mammals, auditory hair cells lose their kinocilium with maturity.

作为毛束的一部分，前庭毛细胞（见图 15-15B）有一个大的肌纤毛，它是一个真正的纤毛，具有微管的特征性 9 + 2 模式（见图 2-11C）。肌基纤毛的作用尚不清楚。在哺乳动物中，听觉毛细胞会随着成熟而失去纤毛。

Both vestibular and auditory hair cells have 50 to 150 stereovilli, which are filled with actin and are more akin to microvilli. The stereovilli—often called stereocilia, although they lack the typical 9 + 2 pattern of true cilia—are 0.2 to 0.8 μm in diameter and are generally 4 to 10 μm in height. These “hairs” are arranged in a neat array. In the vestibular system, the kinocilium stands tallest along one side of the bundle and the stereovilli fall away in height to the opposite side (see Fig. 15-15B). Stereovilli are narrower at their base and insert into the apical membrane of the hair cell, where they make a sort of hinge before connecting to a cuticular plate. Within the bundle, stereovilli are connected one to the next, but they can slide with respect to each other as the bundle is deflected side to side. The ends of the stereovilli are interconnected with very fine strands called tip links, which are visible by electron microscopy.

前庭和听觉毛细胞都有 50 到 150 个立体绒毛，它们充满了肌动蛋白，更类似于微绒毛。立体绒毛（通常称为立体纤毛，尽管它们缺乏真纤毛的典型 9 + 2 模式）直径为 0.2 至 0.8 μm，高度通常为 4 至 10 μm。这些 “头发” 排列整齐。在前庭系统中，肌束一侧的纤毛最高，而立体绒毛的高度下降到另一侧（见图 15-15B）。立体绒毛的基部较窄，并插入毛细胞的顶膜，在连接到表皮板之前，它们在那里形成一种铰链。在线束内，立体绒毛彼此相连，但当线束左右偏转时，它们可能会相互滑动。立体绒毛的末端与称为尖端链节的非常细的链相互连接，这些链可以通过电子显微镜看到。

The epithelium of which the hair cells are a part separates perilymph from endolymph. The perilymph bathes the basolateral side of the hair cells. In composition (i.e., relatively low [K+], high [Na+]), perilymph is similar to CSF. Its voltage is zero—close to that of most other extracellular fluids in the body. The basolateral resting potential of vestibular hair cells and auditory inner hair cells is about −40 mV (see Fig. 15-15B). The endolymph bathing the stereovilli is singular in composition. It has a very high [K+] (150 mM) and a very low [Na+] (1 mM), more like cytoplasm than extracellular fluid. It also has a relatively high [HCO3−] (30 mM). The voltage of the vestibular endolymph is ~0 mV relative to perilymph. Across the apical membrane of vestibular hair cells, the chemical gradient for K+ is small. However, the electrical gradient is fairly large, ~40 mV. Thus, a substantial force tends to drive K+ into the vestibular hair cell across the apical membrane. We will see that the driving force for K+ influx is even higher in the auditory system (see p. 378). The appropriate stimulus for a hair cell is the bending of its hairs, but not just any deflection will do. Bending of the hair bundle toward the longer stereovilli (Fig. 15-16A) excites the cell and causes a depolarizing receptor potential (see pp. 353–354). Bending of the hair bundle away from the longer stereovilli (see Fig. 15-16B) hyperpolarizes the cell. Only tiny movements are needed. In auditory hair cells, as little as 0.5 nm (which is the diameter of a large atom) gives a detectable response, and the response is saturated at ~150 nm, about the diameter of one stereovillus or 1 degree of angular deflection! In fact, the sensitivity of hair cells is limited only by noise from the brownian motion of surrounding molecules. The cell is also exquisitely selective to direction. If the hairs are bent along the axis 90 degrees to their preferred direction, they are less than one tenth as responsive.

毛细胞所属的上皮将外淋巴液与内淋巴液分开。外淋巴液沐浴在毛细胞的基底外侧。在成分上（即相对较低的 [K+]、较高的 [Na+]），外淋巴液与 CSF 相似。它的电压为零——接近体内大多数其他细胞外液的电压。前庭毛细胞和听觉内毛细胞的基底外侧静息电位约为 -40 mV（见图 15-15B）。沐浴立体绒毛的内淋巴液在成分上是单一的。它具有非常高的 [K+] （150 mM）和非常低的 [Na+] （1 mM），更像细胞质而不是细胞外液。它还具有相对较高的 [HCO3−] （30 mM）。前庭内淋巴液的电压相对于外淋巴液为 ~0 mV。穿过前庭毛细胞的顶膜，K+ 的化学梯度很小。但是，电梯度相当大，为 ~40 mV。因此，很大的力倾向于将 K+ 穿过顶膜进入前庭毛细胞。我们将看到 K+ 内流的驱动力在听觉系统中甚至更高（见第 378 页）。对毛细胞的适当刺激是它的毛发弯曲，但不仅仅是任何偏转都可以。发束向较长的立体绒毛弯曲（图 15-16A）会激发细胞并导致去极化受体电位（参见第 353-354 页）。发束从较长的立体绒毛弯曲（见图 15-16B）使细胞超极化。只需要微小的动作。在听觉毛细胞中，低至 0.5 nm（这是一个大原子的直径）就会产生可检测的响应，并且响应在 ~150 nm 处饱和，大约是一个立体绒毛的直径或 1 度的角度偏转！事实上，毛细胞的灵敏度仅受周围分子布朗运动噪声的限制。该单元对方向也有极好的选择性。如果头发沿轴向其首选方向弯曲 90 度，则它们的响应速度不到十分之一。

Mechanotransduction in hair cells seems to be accomplished by directly linking the movement of the stereovilli to the gating of apical mechanosensitive cation channels. Electrical measurements, as well as the imaging of intracellular Ca2+, imply that the transduction channels are located near the tips of the stereovilli. How is channel gating connected to movement of the hairs? The latency of channel opening is extremely short, <40 μs. If one deflects the hairs more rapidly, the channels are activated more quickly. This observation suggests a direct, physical coupling inasmuch as diffusion of a second messenger would take much longer. Corey and Hudspeth have suggested a spring-like molecular linkage between the movement of stereovilli and channel gating. The tip links may be the tethers between stereovilli and the channels, with the channels located at the lower ends of the tip links. Tip links themselves are formed from two types of cadherins, cadherin 23 and protocadherin 15, which form strands of high stiffness. Brief exposure to low- Ca2+ solutions destroys the tip links, without otherwise causing obvious harm to the cells, and thereby abolishes transduction.

毛细胞中的机械转导似乎是通过将立体绒毛的运动与顶端机械敏感阳离子通道的门控直接联系起来来完成的。电学测量以及细胞内 Ca2+ 的成像表明转导通道位于立体绒毛尖端附近。通道门控如何与毛发的运动相关联？通道打开的延迟极短，<40 μs。如果更快地偏转头发，则通道会更快地激活。这一观察表明了直接的物理耦合，因为第二个信使的扩散需要更长的时间。Corey 和 Hudspeth 提出了立体绒毛的运动和通道门控之间存在弹簧状分子联系。尖端链接可以是立体绒毛和通道之间的系绳，通道位于尖端链接的下端。尖端链接本身由两种类型的钙粘蛋白形成，即钙粘蛋白 23 和原钙粘蛋白 15，它们形成高刚度的链。短暂暴露于低 Ca2+ 溶液会破坏尖端链接，而不会对细胞造成明显伤害，从而消除转导。

The mechanosensitive channels at the tips of the stereovilli are nonselective cation channels with relatively large unitary conductances (150 to 300 picosiemens, depending on hair cell type), allowing monovalent and some divalent cations, including Ca2+, to pass easily. Each stereovillus has no more than two channels, which makes their identification elusive. Under physiological conditions, K+ carries most of the current through the transduction channels. When the cell is at rest—hairs straight up—a small but steady leak of depolarizing K+ current flows through the cell. This leak allows the hair cell to respond to both positive and negative deflections of its stereovilli. A positive deflection—toward the tallest stereovilli—further opens the apical channels, leading to influx of K+ and thus depolarization. K+ leaves the cell through mechanoinsensitive K+ channels on the basolateral side (see Fig. 15-16A), along a favorable electrochemical gradient. A negative deflection closes the apical channels and thus leads to hyperpolarization (see Fig. 15-16B).

立体绒毛尖端的机械敏感通道是非选择性阳离子通道，具有相对较大的幺正电导（150 至 300 皮秒，取决于毛细胞类型），允许一价和一些二价阳离子（包括 Ca2+）轻松通过。每个立体绒毛不超过两个通道，这使得它们的识别变得难以捉摸。在生理条件下，K+ 通过转导通道携带大部分电流。当细胞处于静止状态时（头发笔直向上），一小块但稳定的去极化 K+ 电流泄漏流过细胞。这种泄漏使毛细胞能够对其立体绒毛的正向和负向偏转做出反应。正偏转 - 朝向最高的立体绒毛 - 进一步打开顶端通道，导致 K+ 流入，从而去极化。K+ 通过基底外侧的机械不敏感 K+ 通道离开细胞（见图 15-16A），沿着有利的电化学梯度。负偏转会关闭顶端通道，从而导致超极化（见图 15-16B）。

A hair cell is not a neuron. Hair cells do not project axons of their own, and most do not generate action potentials. Instead—in the case of vestibular hair cells and auditory inner hair cells—the membrane near the presynaptic (i.e., basolateral) face of the cell has voltage-gated Ca2+ channels that are somewhat active at rest but more active during mechanically induced depolarization (i.e., the receptor potential) of the hair cell. The Ca2+ that enters the hair cell through these channels triggers the graded release of glutamate as well as aspartate in the case of vestibular hair cells. These excitatory transmitters stimulate the postsynaptic terminal of sensory neurons that transmit information to the brain. The greater the transmitter release, the greater the rate of action potential firing in the postsynaptic axon.

毛细胞不是神经元。毛细胞不会投射自己的轴突，并且大多数不会产生动作电位。相反，在前庭毛细胞和听觉内毛细胞的情况下，细胞突触前（即基底外侧）表面附近的膜具有电压门控 Ca2+ 通道，这些通道在静止时有些活跃，但在机械诱导的毛细胞去极化（即受体电位）期间更活跃。通过这些通道进入毛细胞的 Ca2+ 在前庭毛细胞的情况下触发谷氨酸和天冬氨酸的逐渐释放。这些兴奋性递质刺激将信息传递到大脑的感觉神经元的突触后末梢。递质释放的次数越多，突触后轴突中的动作电位放电速率就越大。

In mammals, all hair cells—whether part of the vestibular or auditory system—are contained within bilateral sets of interconnected tubes and chambers called, appropriately enough, the membranous labyrinth (Fig. 15-17). The vestibular portion has five sensory structures: two otolithic organs, which detect gravity (i.e., head position) and linear head movements, and three semicircular canals, which detect head rotation. Also contributing to our sense of spatial orientation and motion are proprioceptors (see pp. 383–389) and the visual system (see pp. 359–371). N15-5 The auditory portion of the labyrinth is the spiraling cochlea, which detects rapid vibrations (sound) transmitted to it from the surrounding air.

在哺乳动物中，所有毛细胞——无论是前庭系统还是听觉系统的一部分——都包含在双侧相互连接的管子和腔室中，这些管子和腔室恰如其分地称为膜迷路（图 15-17）。前庭部分有五个感觉结构：两个耳石器官，检测重力（即头部位置）和线性头部运动，以及三个半规管，检测头部旋转。本体感受器（见第 383-389 页）和视觉系统（见第 359-371 页）也有助于我们的空间定位和运动感。N15-5 迷路的听觉部分是螺旋状的耳蜗，它能检测到从周围空气传来的快速振动（声音）。

The ultimate function of each of these sensory structures is to transmit mechanical energy to their hair cells. In each case, transduction occurs in the manner described above. The specificity of the transduction process depends much less on the hair cells than on the structure of the labyrinth organs around them.

这些感觉结构的最终功能是将机械能传递给它们的毛细胞。在每种情况下，转导都以上述方式发生。转导过程的特异性对毛细胞的依赖程度远不取决于它们周围迷宫器官的结构。

1.2 耳石器官（球囊和椭圆囊）检测头部的方向和线性加速度

The otolithic organs (saccule and utricle) detect the orientation and linear acceleration of the head

The otolithic organs are a pair of relatively large chambers— the saccule and the utricle—near the center of the labyrinth (see Fig. 15-17B). These otolithic organs as well as the semicircular canals are (1) lined by epithelial cells, (2) filled with endolymph, (3) surrounded by perilymph, and (4) encased in the temporal bone. Within the epithelium, specialized vestibular dark cells secrete K+ and are responsible for the high [K+] of the endolymph. The mechanism of K+ secretion is similar to that by the stria vascularis in the auditory system (see p. 378).

耳石器官是一对相对较大的腔室——球囊和椭圆囊——靠近迷路中心（见图 15-17B）。这些耳石器官以及半规管（1）由上皮细胞排列，（2）充满内淋巴，（3）被外淋巴包围，以及（4）包裹在颞骨中。在上皮细胞内，专门的前庭暗细胞分泌 K+，并负责内淋巴液的高 [K+]。K+ 分泌的机制与听觉系统中血管纹的分泌机制相似（见第 378 页）。

The saccule and utricle each have a sensory epithelium called the macula, which contains the hair cells that lie among a bed of supporting cells. The stereovilli project into the gelatinous otolithic membrane, a mass of mucopolysaccharides that is studded with otoliths or otoconia (Fig. 15-18A, B). Otoconia are crystals of calcium carbonate, 1 to 5 μm in diameter, that give the otolithic membrane a higher density than the surrounding endolymph. With either a change in the angle of the head or a linear acceleration, the inertia of the otoconia causes the otolithic membrane to move slightly, deflecting the stereovilli.

球囊和椭圆囊各有一个称为黄斑的感觉上皮，其中包含位于支持细胞床中的毛细胞。立体绒毛投射到凝胶状耳石膜中，这是一团粘多糖，上面布满耳石或耳石（图 15-18A、B）。耳石菌是直径为 1 至 5 μm 的碳酸钙晶体，使耳石膜的密度高于周围的内淋巴液。随着头部角度的变化或线性加速度，耳石的惯性导致耳石膜轻微移动，使立体绒毛偏转。

The macula is vertically oriented (in the sagittal plane) within the saccule and horizontally oriented within the utricle when the head is tilted down by ~25 degrees, as during walking. Recall that hair cells are depolarized or hyperpolarized when stereovilli bend toward or away from the kinocilium, respectively (see Fig. 15-16). In the saccule, the kinocilia point away from a curving reversal line that divides the macula into two regions (see Fig. 15-18D). In the utricle, the kinocilia point toward the reversal line. The hair cells of the saccule and utricle respond well to changes in head angle and to acceleration of the sort that is experienced as a car or an elevator starts or stops. Of course, the head can tilt or experience acceleration in many directions. Indeed, the orientations of hair cells of the saccule and utricle covers a full range of directions. Any tilt or linear acceleration of the head will enhance the stimulation of some hair cells, reduce the stimulation of others, and have no effect on the rest.

当头部向下倾斜 ~25 度时，黄斑在球囊内垂直定向（在矢状面上），在椭圆囊内水平定向，就像在行走时一样。回想一下，当立体绒毛分别朝向或远离纤毛弯曲时，毛细胞会去极化或超极化（见图 15-16）。在球囊中，金纤毛指向远离将黄斑分成两个区域的弯曲反转线（见图 15-18D）。在椭圆囊中，金纤毛指向反转线。球囊和椭圆囊的毛细胞对头部角度的变化和汽车或电梯启动或停止时所经历的那种加速度反应良好。当然，头部可以向多个方向倾斜或经历加速度。事实上，球囊和椭圆囊的毛细胞方向涵盖了所有方向。头部的任何倾斜或线性加速度都会增强对某些毛细胞的刺激，减少对其他毛细胞的刺激，而对其余毛细胞没有影响。

Each hair cell synapses on the ending of a primary sensory axon that is part of the vestibular nerve, which in turn is a branch of the vestibulocochlear nerve (CN VIII). The cell bodies of these sensory neurons are located in Scarpa’s ganglion within the temporal bone. The dendrites project to multiple hair cells, which increases the signal-to-noise ratio. The axons project to the ipsilateral vestibular nucleus in the brainstem. N15-6 Because the saccule and utricle are paired structures (one on each side of the head), the CNS can simultaneously use information encoded by the full population of otolithic hair cells and unambiguously interpret any angle of tilt or linear acceleration. The push-pull arrangement of increased/decreased activity within each macula (for hair cells of opposite orientation) and between maculae on either side of the head enhances the fidelity of the signal.

每个毛细胞突触位于初级感觉轴突的末端，该轴突是前庭神经的一部分，而前庭神经又是前庭耳蜗神经（CN VIII）的一个分支。这些感觉神经元的细胞体位于颞骨内的 Scarpa 神经节中。树突投射到多个毛细胞上，这增加了信噪比。轴突投射到脑干的同侧前庭核。N15-6 因为球囊和椭圆囊是成对的结构（头部两侧各一个），所以 CNS 可以同时使用由整个耳石毛细胞群编码的信息，并明确解释任何倾斜角度或线性加速度。每个黄斑内（对于相反方向的毛细胞）和头部两侧黄斑之间活动增加/减少的推拉排列增强了信号的保真度。

1.3 半规管检测头部的角加速度

The semicircular canals detect the angular acceleration of the head

Semicircular canals (see Fig. 15-17B) also sense acceleration, but not the linear acceleration that the otolithic organs prefer. Angular acceleration generated by sudden head rotations is the primary stimulus for the semicircular canals. Shake your head side to side or nod it up and down. Each rotation of your head will excite some of your canals and inhibit others.

半规管（见图 15-17B）也可以感应到加速度，但不能感应耳石器官喜欢的线性加速度。头部突然旋转产生的角加速度是半规管的主要刺激。左右摇头或上下点头。你的头每旋转一次都会刺激你的一些耳道并抑制其他耳道。

The semicircular canals stimulate their hair cells differently than the otolithic organs. In each canal, the hair cells are clustered within a sensory epithelium (the crista ampullaris) that is located in a bulge along the canal called the ampulla (see Fig. 15-18C). The hair bundles—all of which have the same orientation—project into a gelatinous, domeshaped structure called the cupula, which spans the lumen of the ampulla. The cupula contains no otoconia, and its mucopolysaccharides have the same density as the surrounding endolymph. Thus, the cupula is not sensitive to linear acceleration. However, with a sudden rotation of the canal, the endolymph tends to stay behind because of its inertia. N15-4 The endolymph exerts a force on the movable cupula, much like wind on a sail. This force bows the cupula, which bends the hairs and (depending on the direction of rotation) either excites or suppresses the release of transmitter from the hair cells onto the sensory axons of the vestibular nerve. This arrangement makes the semicircular canals very sensitive to angular acceleration of the head. N15-7

半规管刺激其毛细胞的方式与耳石器官不同。在每个管中，毛细胞聚集在感觉上皮（壶腹嵴）内，该感觉上皮位于沿根管的凸起中，称为壶腹（见图 15-18C）。这些发束（所有发束都具有相同的方向）投射成一个称为壶腹的凝胶状圆顶状结构，该结构跨越壶腹腔。壶腹菌不含耳石，其粘多糖与周围的内淋巴液具有相同的密度。因此，壶腹帽对线性加速度不敏感。然而，随着根管的突然旋转，由于其惯性，内淋巴液往往会留在后面。N15-4 内淋巴液对可移动的壶腹肌施加力，很像风吹在帆上。这种力使壶盖弯曲，使毛发弯曲并（取决于旋转方向）激发或抑制从毛细胞释放到前庭神经感觉轴突上的递质。这种排列使半规管对头部的角加速度非常敏感。编号 N15-7

Each side of the head has three semicircular canals that lie in approximately orthogonal planes. The anterior canal is tilted ~41 degrees anterolaterally from the sagittal plane, the posterior canal is tilted ~56 degrees posterolaterally from the sagittal plane, and the lateral canal is tipped ~25 degrees back from the horizontal plane. Because each canal best senses rotation about a particular axis, the three together give a good representation of all possible angles of head rotation. This complete representation is further ensured because each canal is paired with another on the opposite side of the head. Each member of a pair sits within the same plane and responds to rotation about the same axis. However, whereas rotation excites the hair cells of one canal, it inhibits the canals of its contralateral axis mate. This push-pull arrangement presumably increases the sensitivity of detection.

头部的每一侧都有三个半规管，位于大致正交的平面上。前管从矢状面向前外侧倾斜 ~41 度，后管从矢状面向后外侧倾斜 ~56 度，外侧管从水平面向后倾斜 ~25 度。因为每个耳道最能感知围绕特定轴的旋转，所以这三个管一起可以很好地表示头部旋转的所有可能角度。这种完整的表示得到了进一步的保证，因为每个根管都与头部另一侧的另一个根管配对。对中的每个成员都位于同一平面内，并响应绕同一轴的旋转。然而，虽然旋转会激发一个管的毛细胞，但它会抑制其对侧轴配合的根管。这种推挽式布置可能增加了检测的灵敏度。

1.4 外耳和中耳收集和调节气压波，以便在内耳内进行转导

The outer and middle ears collect and condition air pressure waves for transduction within the inner ear

1.5 耳蜗是由三根平行的、充满液体的管子组成的螺旋形

The cochlea is a spiral of three parallel, fluid-filled tubes

The auditory portion of the inner ear is mainly the cochlea, a tubular structure that is ~35 mm long and is coiled 2.5 times into a snail shape about the size of a large pea (Fig. 15-20). Counting its stereovilli, the cochlea has a million moving parts, which makes it the most complex mechanical apparatus in the body.

内耳的听觉部分主要是耳蜗，耳蜗是一种管状结构，长 ~35 毫米，盘绕 2.5 次，呈蜗牛形，大约有大豌豆大小（图 15-20）。算上它的立体绒毛，耳蜗有 100 万个活动部件，这使其成为人体中最复杂的机械装置。

The cut through the cochlea in the lower left drawing in Figure 15-20 reveals five cross sections of the spiral. We see that in each cross section, two membranes divide the cochlea into three fluid-filled compartments. On one side is the compartment called the scala vestibuli (see Fig. 15-20, right side), which begins at its large end near the oval window— where vibrations enter the inner ear. Reissner’s membrane separates the scala vestibuli from the middle compartment, the scala media. The other boundary of the scala media is the basilar membrane, on which rides the organ of Corti and its hair cells. Below the basilar membrane is the scala tympani, which terminates at its basal or large end at the round window. Both the oval and round windows look into the middle ear (see Fig. 15-19B).

图 15-20 中左下角图中穿过耳蜗的切口显示了螺旋线的五个横截面。我们看到，在每个横截面中，两个膜将耳蜗分成三个充满液体的隔室。一侧是称为前庭鳞片的隔室（见图 15-20，右侧），它从靠近椭圆形窗口的大端开始——振动进入内耳。Reissner 膜将前庭标片与中间隔室（标片介质）隔开。鳞片介质的另一个边界是基底膜，其上覆盖着 Corti 器官及其毛细胞。基底膜下方是鼓膜，其终止于圆窗的基端或大端。椭圆形和圆形窗口都可以看到中耳（见图 15-19B）。

Both the scala vestibuli and scala tympani are lined by a network of fibrocytes and filled with perilymph (see pp. 372–373). Like its counterpart in the vestibular system, this perilymph is akin to CSF (i.e., low [K+], high [Na+]). Along the lengths of scala vestibuli and scala tympani, the two perilymphs communicate through the leaky interstitial fluid spaces between the fibrocytes. At the apex of the cochlea, the two perilymphs communicate through a small opening called the helicotrema. Cochlear perilymph communicates with vestibular perilymph through a wide passage at the base of the scala vestibuli (see Fig. 15-17B), and it communicates with the CSF through the cochlear aqueduct.

前庭鳞片和鼓膜鳞片都由纤维细胞网络衬垫，并充满外淋巴液（见第 372-373 页）。与前庭系统中的对应物一样，这种外淋巴液类似于 CSF（即低 [K+]、高 [Na+]）。沿着前庭鳞片和鼓膜鳞的长度，两个外淋巴液通过纤维细胞之间渗漏的间质液空间进行交流。在耳蜗的顶端，两个外淋巴液通过一个称为螺旋线的小开口进行交流。耳蜗外淋巴液通过前庭鳞片底部的宽通道与前庭外淋巴液相通（见图 15-17B），并通过耳蜗导水管与 CSF 相通。

The scala media is filled with endolymph. Like its vestibular counterpart—with which it communicates through the ductus reuniens (see Fig. 15-17B)—auditory endolymph is extremely rich in K+. Unlike vestibular endolymph, which has the same voltage as the perilymph, auditory endolymph has a voltage of +80 mV relative to the perilymph (see Fig. 15-20, right side). This endocochlear potential, which is the highest transepithelial voltage in the body, is the main driving force for sensory transduction in both inner and outer hair cells. Moreover, loss of the endocochlear potential is a frequent cause of hearing loss. A highly vascularized tissue called the stria vascularis secretes the K+ into the scala media, and the resulting K+ gradient between endolymph and perilymph generates the strong endocochlear potential.

鳞片中层充满内淋巴液。就像它的前庭对应物一样——它通过联合管与之交流（见图 15-17B）——听觉内淋巴液富含 K+。与具有与外淋巴液相同电压的前庭内淋巴液不同，听觉内淋巴液相对于外淋巴液的电压为 +80 mV（见图 15-20，右侧）。这种耳蜗电位是体内最高的跨上皮电压，是内毛细胞和外毛细胞感觉转导的主要驱动力。此外，耳蜗内电位的丧失是听力损失的常见原因。一种称为血管纹的高度血管化组织将 K+ 分泌到鳞片中，由此产生的内淋巴液和外淋巴液之间的 K+ 梯度产生强的耳蜗电位。

The stria vascularis is functionally a two-layered epithelium (Fig. 15-21). Marginal cells separate endolymph from a very small intrastrial compartment inside the stria vascularis, and basal cells separate the intrastrial compartment from the interstitial fluid of the spiral ligament, which is contiguous with perilymph. Gap junctions connect one side of the basal cells to intermediate cells and the other side of the basal cells to fibrocytes of the spiral ligament. This architecture is essential for generation of the endocochlear potential.

血管纹在功能上是一个两层上皮（图 15-21）。边缘细胞将内淋巴液与血管纹内一个非常小的心房内隔室分开，基底细胞将心室内隔室与螺旋韧带的间质液分开，螺旋韧带与外淋巴液相邻。间隙连接将基底细胞的一侧连接到中间细胞，将基底细胞的另一侧连接到螺旋韧带的纤维细胞。这种结构对于耳蜗电位的产生至关重要。

The fibrocytes are endowed with K+ uptake mechanisms that maintain a high [K+]i in the intermediate cells. The KCNJ10 K+ channel of the intermediate cells generates the endocochlear potential. The K+ equilibrium potential of these cells is extremely negative because of the combination of their very high [K+]i and the very low [K+] of the intrastrial fluid. Finally, the marginal cells support the endocochlear potential by mopping up the K+ from the intrastrial fluid— keeping the intrastrial [K+] very low—and depositing the K+ in the endolymph through a KCNQ1 K+ channel.

纤维细胞具有 K+ 摄取机制，可在中间细胞中维持高 [K+]i。中间细胞的 KCNJ10 K+ 通道产生耳蜗电位。这些细胞的 K+ 平衡电位是极负的，因为它们的 [K+]i 非常高，而室内液的 [K+] 非常低。最后，边缘细胞通过从房内液中清除 K+（保持房内 [K+] 非常低）并通过 KCNQ1 K+ 通道将 K+ 沉积在内淋巴液中来支持耳蜗内电位。

1.6 内毛细胞转导声音，而外毛细胞的主动运动会放大信号

Inner hair cells transduce sound, whereas the active movements of outer hair cells amplify the signal

1.7 听觉毛细胞的频率灵敏度取决于它们沿耳蜗基底膜的位置

The frequency sensitivity of auditory hair cells depends on their position along the basilar membrane of the cochlea

The subjective experience of tonal discrimination is called pitch. Young humans can hear sounds with frequencies from ~20 to 20,000 Hz. N15-13 This range is modest by the standards of most mammals because many hear up to 50,000 Hz, and some, notably whales and bats, can hear sounds with frequencies >100,000 Hz.

声调辨别的主观体验称为音高。年轻人可以听到频率在 ~20 到 20,000 Hz 之间的声音。N15-13 以大多数哺乳动物的标准来看，这个范围是适中的，因为许多哺乳动物听到的声音高达 50,000 Hz，而有些动物，特别是鲸鱼和蝙蝠，可以听到频率> 100,000 Hz 的声音。

A continuous pure tone (see p. 376) produces a wave that travels along the basilar membrane and has different amplitudes at different points along the base-apex axis (Fig. 15-24A). Increases in sound amplitude cause an increase in the rate of action potentials in auditory nerve axons—rate coding. N15-14 The frequency of the sound determines where along the cochlea the cochlear membranes vibrate most—high frequencies at one end and low at the other— and thus which hair cells are stimulated. This selectivity is the basis for place coding in the auditory system; that is, the frequency selectivity of a hair cell depends mainly on its longitudinal position along the cochlear membranes. The cochlea is essentially a spectral analyzer that evaluates a complex sound according to its pure tonal components, with each pure tone stimulating a specific region of the cochlea.

连续的纯音（见第 376 页）产生一个沿基底膜传播的波，并在沿基顶点轴的不同点具有不同的振幅（图 15-24A）。声音振幅的增加会导致听觉神经轴突中动作电位速率的增加——速率编码。N15-14 声音的频率决定了耳蜗膜在耳蜗上振动最剧烈的位置（一端高频，另一端低频），从而决定了哪些毛细胞受到刺激。这种选择性是听觉系统中位置编码的基础;也就是说，毛细胞的频率选择性主要取决于其沿耳蜗膜的纵向位置。耳蜗本质上是一个频谱分析器，它根据其纯音调成分评估复杂的声音，每个纯音都刺激耳蜗的特定区域。

Using optical methods to study cadaver ears, Georg von Békésy found that sounds of a particular frequency generate relatively localized waves in the basilar membrane and that the envelope of these waves changes position according to the frequency of the sound (see Fig. 15-24B). Low frequencies generate their maximal amplitudes near the apex. As sound frequency increases, the envelope shifts progressively toward the basal end (i.e., near the oval and round windows). For his work, von Békésy N15-15 received the 1961 Nobel Prize in Physiology or Medicine.

使用光学方法研究尸体的耳朵，Georg von Békésy 发现特定频率的声音在基底膜中产生相对局部的波，并且这些波的包络根据声音的频率改变位置（见图 15-24B）。低频在顶点附近产生最大振幅。随着声音频率的增加，包络逐渐向基端移动（即靠近椭圆形和圆形窗口）。由于他的工作，von Békésy N15-15 获得了 1961 年诺贝尔生理学或医学奖。

Two properties of the basilar membrane underlie the low-apical to high-basal gradient of resonance: taper and stiffness (see Fig. 15-24C). If we could unwind the cochlea and stretch it straight, we would see that it tapers from base to apex. The basilar membrane tapers in the opposite direction—wider at the apex, narrower at the base. More important, the narrow basal end is ~100-fold stiffer than its wide and floppy apical end. Thus, the basilar membrane resembles a harp. At one end—the base, near the oval and round windows—it has short, taut strings that vibrate at high frequencies. At the other end—the apex—it has longer, looser strings that vibrate at low frequencies. Although von Békésy’s experiments were illuminating, they were also paradoxical. A variety of experimental data suggested that the tuning of living hair cells is considerably sharper than the broad envelopes of von Békésy’s traveling waves on the basilar membrane could possibly produce. N15-16 Recordings from primary auditory nerve cells are also very sharp, implying that this tuning must occur within the cochlea, not in the CNS. Some enhancement of tuning comes from the structure of the inner hair cells themselves. Those near the base have shorter, stiffer stereovilli, which makes them resonate to higher frequencies than possible with the longer, floppier stereovilli on cells near the apex. The blue curve in Figure 15-25 approximates von Békésy’s envelope of traveling waves for a passive basilar membrane from cadavers. It is important to note that von Békésy used unnaturally loud sounds. With reasonable sound levels, the maximum passive displacement of the basilar membrane would be slightly more than 0.1 nm. This distance is less than the pore diameter of an ion channel and also less than the threshold (0.3 to 0.4 nm) for an electrical response from a hair cell. However, measurements from the basilar membrane in living animals (the orange curve in Fig. 15-25) by very sensitive methods show that movements of the basilar membrane are much more localized and much larger than predicted by von Békésy. The maximal physiological displacement is ~20-fold greater than threshold and ~40-fold greater than that predicted by the passive von Békésy model. Moreover, the physiological displacement decays sharply on either side of the peak, >100-fold within ~0.5 mm (recall that the human basilar membrane has a total length of >30 mm).

基底膜的两个特性是共振的低顶端到高基底梯度的基础：锥度和刚度（见图 15-24C）。如果我们能解开耳蜗并将其伸直，我们会看到它从基部到顶端逐渐变细。基底膜向相反方向逐渐变细——顶端较宽，基部较窄。更重要的是，狭窄的基端比其宽而松软的顶端硬 ~100 倍。因此，基底膜类似于竖琴。在一端 - 底座，靠近椭圆形和圆形窗口 - 它有短而紧的琴弦，在高频下振动。在另一端 - 顶点 - 它有更长、更松散的琴弦，在低频下振动。尽管 von Békésy 的实验具有启发性，但它们也是自相矛盾的。各种实验数据表明，活毛细胞的调谐比基底膜上 von Békésy 行波的宽包络可能产生的要尖锐得多。N15-16 来自初级听觉神经细胞的记录也非常清晰，这意味着这种调整必须发生在耳蜗内，而不是在 CNS 中。调音的一些增强来自内毛细胞本身的结构。那些靠近基部的具有更短、更硬的立体绒毛，这使得它们比在靠近顶点的单元上较长、更松软的立体绒毛能产生更高的频率共振。图 15-25 中的蓝色曲线近似于尸体被动基底膜的 von Békésy 行波包络。值得注意的是，von Békésy 使用了不自然的响亮声音。在合理的声级下，基底膜的最大被动位移将略大于 0.1 nm。该距离小于离子通道的孔径，也小于毛细胞电响应的阈值（0.3 至 0.4 nm）。然而，通过非常敏感的方法对活体动物的基底膜（图 15-25 中的橙色曲线）进行的测量表明，基底膜的运动比 von Békésy 预测的要局限得多，也大得多。最大生理位移比阈值大 ~20 倍，比被动 von Békésy 模型预测的 ~40 倍大。此外，生理位移在峰的两侧急剧衰减，在 ~0.5 mm 内> 100 倍（回想一下，人基底膜的总长度为 >30 mm）。

Both the extremely large physiological excursions of the basilar membrane and the exquisitely sharp tuning of the cochlea depend on the cochlear amplifier (see p. 380). Indeed, selectively damaging outer hair cells—with large doses of certain antibiotics, for example—considerably dulls the sharpness of cochlear tuning and dramatically reduces the amplification.

基底膜的极大生理偏移和耳蜗的精致尖锐的调谐都取决于耳蜗放大器（见第 380 页）。事实上，选择性地破坏外毛细胞（例如，使用大剂量的某些抗生素）会大大减弱人工耳蜗调谐的清晰度，并显着降低放大。

The brain can control the tuning of hair cells. Axons that arise in the superior olivary complex in the brainstem synapse mainly on the outer hair cells and, sparsely, on the afferent axons that innervate the inner hair cells. N15-17 Stimulation of these olivocochlear efferent fibers suppresses the responsiveness of the cochlea to sound and is thought to provide auditory focus by suppressing responsiveness to unwanted sounds—allowing us to hear better in noisy environments (Box 15-2). The main efferent neurotransmitter is acetylcholine (ACh), which activates ionotropic ACh receptors (see pp. 206–207)—nonselective cation channels—and triggers an entry of Ca2+. The influx of Ca2+ activates Ca2+-activated K+ channels, causing a hyperpolarization—effectively an inhibitory postsynaptic potential—that suppresses the electromotility of outer hair cells and action potentials in afferent dendrites. Thus, the efferent axons allow the brain to control the gain of the inner ear.

大脑可以控制毛细胞的调整。出现在脑干突触上橄榄复合体中的轴突主要在外毛细胞上，稀疏地出现在支配内毛细胞的传入轴突上。N15-17 刺激这些橄榄耳蜗传出纤维会抑制耳蜗对声音的反应，并被认为通过抑制对不需要的声音的反应来提供听觉焦点——让我们在嘈杂的环境中听得更清楚（框 15-2）。主要的传出神经递质是乙酰胆碱（ACh），它激活离子型 ACh 受体（参见第 206-207 页）——非选择性阳离子通道——并触发 Ca2+ 的进入。Ca2+ 的流入激活了 Ca2+ 激活的 K+ 通道，导致超极化——实际上是一种抑制性突触后电位——从而抑制了外毛细胞的电动性和传入树突中的动作电位。因此，传出轴突允许大脑控制内耳的增益。

2 躯体感觉受体、本体感觉和疼痛

SOMATIC SENSORY RECEPTORS, PROPRIOCEPTION, AND PAIN