Ch15 Sensory Transduction

2024年11月12日 (二) 16:12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

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

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