The cochlea achieves a greater mechanical sensitivity than the vestibular organs. The energy required for this process is provided by the stria vascularis (Figure 44–21). This structure forms the outer wall of the scala media and sits within the spiral ligament. It is highly vascular and metabolically active in order to maintain the high potassium concentration within the scala media. There are tight junctions between the apex of the hair cells and the surrounding supporting cells that form the barrier (the reticular lamina) between the endolymph and the perilymph. The stria vascularis acts as a battery whose electrical current powers hearing. In addition to elevated potassium concentrations, it creates a positive potential within the endolymph relative to the perilymph. This increases the electrochemical gradient that drives a constant flow of K+ ions from the endolymph into the hair cells. This “silent current” is modulated as hair cell stereocilia are deflected. Potassium ions are recycled back to the stria vascularis by diffusion through the perilymph and through supporting cells via gap junctions. The gap junction proteins are called connexins, and mutations of their genes result in sensorineural hearing loss. Connexin mutations are the most common mechanism of genetic hearing loss.
Cross-section of the cochlea. There are three fluid-filled chambers: the scala vestibuli and scala tympani are connected at the apex of the cochlea and contain perilymph; the scala media contains endolymph. The stria vascularis maintains the endolymphatic potential and drives the silent current (arrows) that provides the energy for hearing.
Passive Mechanics Within the Cochlea
The hair cells in the organ of Corti vibrate in response to sound. Differential movements between the basilar membrane and the tectorial membrane bend the stereocilia bundle (see Figure 44–17). In this figure, the flexible basilar membrane is anchored to the bony shelf on the left and a ligament (not shown) on the right. A single flask-shaped inner hair cell is shown on the left, and three rows of cylindrically shaped outer hair cells are seen on the right. The tips of the outer hair cell stereocilia are embedded in a gelatinous mass called the tectorial membrane, which lies on top of the organ of Corti. When sound is transmitted to the inner ear, the organ of Corti vibrates up and down. Since the basilar membrane is attached to bone and ligament at its two ends, the area of maximal vibration is near the third (furthest right) row of outer hair cells. The basilar membrane is fixed at the osseous spiral lamina, whereas the tectorial membrane is fixed at a different position. Movement of the basilar membrane up and down, induced by sound waves within the cochlear fluids, causes a shearing force to deflect the hair cell stereocilia.
The cochlea acts as both a passive and an active filter. Passive filtering produces a traveling wave in response to sound vibrations (Figure 44–22). The location of the peak of the traveling wave changes with the frequency of the sound played into the ear. The change in location results from the tonotopic organization of the organ of Corti. There are systematic differences in its mass and stiffness along its length that determine the frequency response at any specific location. At the base of the cochlea (the high-frequency region), it has a lower mass and a higher stiffness. In contrast, at the apex of the cochlea (the low-frequency region), the organ of Corti has a higher mass and a lower stiffness. Sound vibrations that enter the cochlea at the stapes footplate propagate along the length of the cochlear duct and are maximal when they match the characteristic frequency at a specific location.
The traveling wave. The basilar membrane varies in mass and stiffness along the length of the cochlea (here shown unrolled). This creates a tonotopic organization in which different segments of the basilar membrane are most sensitive to different frequencies. The pressure wave introduced from movement of the stapes propagates up the cochlea and is dissipated at its characteristic frequency place. The cochlea can be modeled as having multiple sections, each with a distinct mass and stiffness of the basilar membrane. (Adapted, with permission, Geisler CD. From Sound to Synapse: Physiology of the Mammalian Ear. New York: Oxford University Press, 1998.)
Active Processes Within the Cochlea
Analyses of the cochlea based only on passive mechanical properties such as mass and stiffness cannot explain the exquisite frequency selectivity of human hearing or the frequency selectivity that is measured from individual auditory nerve fibers. The frequency selectivity of the cochlea is enhanced by an amplification mechanism within the cochlea. The amplification process generates sounds called otoacoustic emissions that can be measured with a sensitive microphone in the ear canal. They are routinely measured in the clinic to assess hearing. The outer hair cell is the amplifier. It elongates and shortens in response to the receptor potential generated by the stereocilia. This is called electromotility. The function of the outer hair cell in hearing is to refine the sensitivity and frequency selectivity of the mechanical vibrations of the cochlea.
Pressurization of the Outer Hair Cells
Most cells have a cytoskeleton to maintain cell shape. Because such an internal skeleton would impede electromotility, a central cytoskeleton is missing in the cylindrical portion of the outer hair cell, thereby improving the cell's flexibility. The outer hair cell must be more than flexible; it must also be strong enough to transmit force to the rest of the organ of Corti. As a result, outer hair cells are pressurized.
Most cells do not tolerate internal pressure because their membrane is weak. The outer hair cell plasma membrane is reinforced with a highly organized actin–spectrin cytoskeleton just underneath the plasma membrane (Figure 44–23). The shape of the outer hair cell is maintained by a pressurized fluid core that pushes against an elastic wall. The lateral wall of the outer hair cell is about 100 nm thick and contains the plasma membrane, the cytoskeleton, and an intracellular organelle called the subsurface cisternae. Particles sit within the plasma membrane and may be related to electromotility. The cytoskeleton consists of actin filaments that are oriented circumferentially around the cell and that are crosslinked by spectrin molecules. Pillar molecules tether the actin–spectrin network to the plasma membrane. The plasma membrane may be rippled between adjacent pillar molecules.
Anatomy of the outer hair cell. The outer hair cell is cylindrical and is divided in three parts. The top part is capped with a cuticular plate into which the stereocilia are inserted. The base of the cell is hemispheric. It contains the cell nucleus and synaptic structures (not shown). The central part of the cell is cylindrical.
Electromotility of Outer Hair Cells
Outer hair cells have a cylindrical shape (Figure 44–24). They vary in length from approximately 12 μm at the basal or high-frequency end of the cochlea to >90 μm at the low-frequency end. Their diameter at all locations is approximately 9 μm. Their apical end is capped with a rigid cuticular plate into which the stereocilia are embedded, and their synaptic end is a hemisphere (compare with the typical hair cell shown in Figure 44–11).
Outer hair cell electromotility. When the mechanoelectrical transduction channels are closed (cell on the left), the outer hair cell is hyperpolarized and elongated. When the channels are open (cell on the right), the outer hair cell is depolarized and shortened. The plasma membrane may flatten and ripple during this process, although this concept is hypothetical. These length changes occur at speeds of up to 100 kHz, and function to amplify the sound pressure waves (the cochlear amplifier). (Adapted, with permission, Synder KV, Sachs F, Brownell WE. The outer hair cell: A mechanoelectrical and electromechanical sensor/actuator. In: Barth FG, Humphrey JAC, Secomb TW, eds. Sensors and Sensing in Biology and Engineering. Wien: Springer-Verlag, 2003.)
Each of these three regions (flat apex, middle cylinder, and hemispheric base) has a specific function. The stereocilia at the apex of the cell are responsible for converting the mechanical energy of sound into electrical energy. Synaptic structures are found at the base of the hair cell and are responsible for converting electrical energy into chemical energy by modulating the release of neurotransmitters. The apex and the base of the outer hair cell perform functions that are common to all hair cells. The elongated cylindrical portion of the outer hair cell is where electrical energy is converted into mechanical energy. This function is unique to the outer hair cell. No other hair cell is able to change its length at acoustic frequencies in response to electrical stimulation. These length changes can be greater than 1% of the cell's original length if the electrical stimulation is large.
The electromotility of the outer hair cells is based on a novel membrane-based motor mechanism in the plasma membrane of the cells' lateral walls. The membrane protein prestin and intracellular chloride ions are required for the motor to work. The mechanical force generated by the membrane is communicated to the ends of the cell by means of an elegant cytoskeletal structure immediately adjacent to the plasma membrane (see Figure 44–23). This motor mechanism is a biological form of piezoelectricity similar to that used in sonar or ultrasound imaging. Both cochlear and vestibular hair cells from humans have similar properties to those of rodents, the animal models in which most research has been done.
Humans are able to discriminate between sounds that are very close in frequency because the outer hair cell acts as the cochlear amplifier. The role of the outer hair cell in hearing is both sensory and mechanical. When the organ of Corti begins to vibrate in response to the incoming sound, each hair cell senses the vibration through the bending of its stereocilia. The bending results in a change in the voltage within the outer hair cell, causing electromotility. If the resulting mechanical force is at the natural frequency of that portion of the cochlea, then the magnitude of the vibration increases. If the electromotile force is at a different frequency, the vibrations decrease. The intact system has greater sensitivity and frequency selectivity than when the outer hair cells are missing or damaged.
One consequence of having an active system is that oscillations can occur even when no energy is coming into the system from the outside. This happens in the cochlea, and the resulting sound vibrations can be measured in the ear canal. These are called spontaneous otoacoustic emissions and are observed only in living ears. Other types of otoacoustic emissions can be measured as well, including distortion product, otoacoustic emissions, and transient evoked otoacoustic emissions. These can be triggered as needed by playing certain types of sound stimuli into the ear and are therefore more useful clinically than the measurement of spontaneous otoacoustic emissions. Measuring otoacoustic emissions has become an important diagnostic tool for determining if outer hair cells are working, particularly in newborn hearing screening (see Chapter 45, Audiologic Testing).
Sensorineural hearing loss is a common clinical problem and has many possible causes, including noise exposure, ototoxicity, and age-related hearing loss (presbycusis). The common site of pathology for all of these conditions within the inner ear is the outer hair cell (see Figure 44–24). The attachments of outer hair cell stereocilia to the tectorial membrane can be broken, even with mild noise exposure. This reduces the ability of outer hair cell electromotility to provide a positive feedback, leading to a temporary hearing loss. With further damage, the actin core of the outer hair cell stereocilia can fracture. With enough trauma, hair cell death occurs and a permanent hearing loss results because mammalian cochlear hair cells do not regenerate. After outer hair cells begin to degenerate, further structures within the cochlea die as well, including inner hair cells, supporting cells, and auditory nerve cells.
A low level of trauma that produces disarray of both inner and outer hair cell stereocilia proportionally elevates eighth nerve tuning curve thresholds (Figure 44–25A). When outer hair cells are lost, only the sharp peak of the tuning curve is lost (Figure 44–25B and D). Loss of inner hair cells produces a dramatic elevation in tuning curve thresholds (Figure 44–25C). Outer hair cell damage blocks the cochlear amplifier, but the passive tuning properties of the cochlea are retained. In contrast, inner hair cell damage reduces cochlear function overall. In summary, outer hair cells are responsible for the cochlear amplifier, whereas inner hair cells provide afferent input.
Various forms of hair cell damage found with noise trauma and their effect on eighth nerve tuning curves. The dotted lines represent normal turning curves and the solid lines are pathologic. (Adapted, with permission, Kiang NY, Liberman MC, Sewell WF, Guinan JJ. Single unit clues to cochlear mechanism. Hear Res. 1986;171.)