The hair cell is an evolutionary triumph that solves the problem of transforming vibrational energy into an electrical signal. The scale at which the hair cell operates is truly amazing: At the limits of human hearing, hair cells can faithfully detect movements of atomic dimensions and respond in the tens of microseconds! Furthermore, hair cells can adapt rapidly to constant stimuli, thus allowing the listener to extract signals from a noisy background.

The hair cell is a flask-shaped epithelial cell named for the bundle of hairlike processes that protrude from its apical end into the scala media. Each hair bundle contains anywhere from 30 to a few hundred hexagonally arranged stereocilia, with one taller kinocilium (Figure 13.7A). Despite their names, only the kinocilium is a true ciliary structure, with the characteristic two central tubules surrounded by nine doublet tubules (Figure 13.7B). The function of the kinocilium is unclear, and in the cochlea of humans and other mammals it actually disappears shortly after birth (Figure 13.7C). The stereocilia are simpler, containing only an actin cytoskeleton. Each stereocilium tapers where it inserts into the apical membrane, forming a hinge about which each stereocilium pivots (Figure 13.7D). The stereocilia are graded in height and are arranged in a bilaterally symmetric fashion (in vestibular hair cells, this plane runs through the kinocilium). Displacement of the hair bundle parallel to this plane toward the tallest stereocilia depolarizes the hair cell, while movements parallel to this plane toward the shortest stereocilia cause hyperpolarization. In contrast, displacements perpendicular to the plane of symmetry do not alter the hair cell's membrane potential. The hair bundle movements at the threshold of hearing are approximately 0.3 nm, about the diameter of an atom of gold!

Figure 13.7

The structure and function of the hair bundle. The vestibular hair bundles shown here resemble those of cochlear hair cells, except for the presence of the kinocilium, which disappears in the mammalian cochlea shortly after birth. (A) The hair bundle (more...)

Hair cells can convert the displacement of the stereociliary bundle into an electrical potential in as little as 10 microseconds; indeed, such speed is required to faithfully transduce high-frequency signals and enable the accurate localization of the source of the sound. The need for microsecond resolution places certain constraints on the transduction mechanism, ruling out the relatively slow second messenger pathways used in visual and olfactory transduction (see Chapters 8, 11 and 15); a direct, mechanically gated transduction channel is needed to operate this quickly. Evidently the filamentous structures that connect the tips of adjacent stereocilia, known as tip links, directly open cation-selective transduction channels when stretched, allowing K⁺ ions to flow into the cell (see Figure 13.7D). As the linked stereocilia pivot from side to side, the tension on the tip link varies, modulating the ionic flow and resulting in a graded receptor potential that follows the movements of the stereocilia (Figure 13.8). The tip link model also explains why only deflections along the axis of the hair bundle activate transduction channels, since tip links join adjacent stereocilia along the axis directed toward the tallest stereocilia (see also Box B in Chapter 14).

Figure 13.8

Mechanoelectrical transduction mediated by hair cells. (A,B) When the hair bundle is deflected toward the tallest stereocilium, cation-selective channels open near the tips of the stereocilia, allowing K⁺ ions to flow into the hair cell down their electrochemical (more...)

Understanding the ionic basis of hair cell transduction has been greatly advanced by intracellular recordings made from these tiny structures. The hair cell has a resting potential between -45 and -60 mV relative to the fluid that bathes the basal end of the cell. At the resting potential, only a small fraction of the transduction channels are open. When the hair bundle is displaced in the direction of the tallest stereocilium, more transduction channels open, causing depolarization as K⁺ enters the cell. Depolarization in turn opens voltage-gated calcium channels in the hair cell membrane, and the resultant Ca²⁺ influx causes transmitter release from the basal end of the cell onto the auditory nerve endings (Figure 13.8A,B). Such calcium-dependent exocytosis is similar to chemical neurotransmission elsewhere in the central and peripheral nervous system (see Chapters 5 and 6). Because some of the transduction channels are open at rest, the receptor potential is biphasic: Movement toward the tallest stereocilia depolarizes the cell, while movement in the opposite direction leads to hyperpolarization. This situation allows the hair cell to generate a sinusoidal receptor potential in response to a sinusoidal stimulus, thus preserving the temporal information present in the original signal up to frequencies of around 3 kHz (Figure 13.8C).

The high speed demands of mechanoelectrical transduction have resulted in some fascinating ionic specializations within the inner ear. An unusual adaptation of the hair cell in this regard is that K⁺ serves both to depolarize and repolarize the cell, enabling the hair cell's K⁺ gradient to be largely maintained by passive ion movement alone. As with other epithelial cells, the basal and apical surfaces of the hair cell are separated by tight junctions, allowing separate extracellular ionic environments at these two surfaces. The apical end is exposed to the K⁺-rich, Na⁺-poor endolymph, which is produced by dedicated ion pumping cells in the stria vascularis (Figure 13.8D). The basal end is bathed in the same fluid that fills the scala tympani, known as perilymph, which resembles other extracellular fluids in that it is K⁺-poor and Na⁺-rich. In addition, the compartment containing endolymph is about 80 mV more positive than the perilymph compartment (this difference is known as the endocochlear potential), while the inside of the hair cell is about 45 mV more negative than the perilymph (and 125 mV more negative than the endolymph). The resulting electrical gradient across the membrane of the stereocilia (about 125 mV) drives K⁺ through open transduction channels into the hair cell, even though these cells already have a high internal K⁺ concentration. K⁺ entry via the transduction channels leads to depolarization of the hair cell, which in turn opens voltage-gated Ca²⁺ and K⁺ channels located in the membrane of the hair cell soma (see Box B in Chapter 14). The opening of somatic K⁺ channels favors K⁺ efflux, and thus repolarization; the efflux occurs because the perilymph surrounding the basal end is low in K⁺ relative to the cytosol, and because the equilibrium potential for K⁺ is more negative than the hair cell's resting potential. Repolarization of the hair cell via K⁺ efflux is also facilitated by Ca²⁺ entry. In addition to modulating the release of neurotransmitter, Ca²⁺ entry opens Ca²⁺-dependent K⁺ channels, which provide another avenue for K⁺ to enter the perilymph. Indeed, the interaction of Ca²⁺ influx and Ca²⁺-dependent K⁺ efflux can lead to electrical resonances that enhance the tuning of response properties within the inner ear (also explained in Box B in Chapter 14). In essence, the hair cell operates as two distinct compartments, each dominated by its own Nernst equilibrium potential for K⁺; this arrangement ensures that the hair cell's ionic gradient will not run down, even during prolonged stimulation. At the same time, compounds such as ethacrynic acid (see Box A), which selectively poison the ion-pumping cells of the stria vascularis, can cause the endocochlear potential to dissipate, resulting in a sensorineural hearing deficit. In short, the hair cell exploits the different ionic milieus of its apical and basal surfaces to provide extremely fast and energy-efficient repolarization.