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Hair Cells

  1. Walter Marcotti1,
  2. Sergio Masetto2

Published Online: 15 JAN 2010

DOI: 10.1002/9780470015902.a0000181.pub2

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How to Cite

Marcotti, W. and Masetto, S. 2010. Hair Cells. eLS. .

Author Information

  1. 1

    University of Sheffield, Department of Biomedical Science, Sheffield, United Kingdom

  2. 2

    University of Pavia, Department of Physiology, Pavia, Italy

Publication History

  1. Published Online: 15 JAN 2010

Introduction: The Inner Ear and Their Sensory Receptors

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

Hearing and balance are key senses that allow humans and other vertebrates to acquire important information from the surrounding environment and to spatially orientate. The receptors responsible for these sensory functions are called hair cells. In fish and some amphibians moreover, the hair cells of the lateral line, an additional sensory organ, are responsible for detecting water movements. See also Ear and Lateral Line of Vertebrates: Organisation and Development

In mammals, auditory hair cells are located all along the spiral structure of the cochlea (Figure 1a) and transduce acoustic stimuli into an electrical response that is relayed to the brain enabling us to perceive sound. Vestibular hair cells are situated in the two otolith organs (the utricle and the sacculus) and three semicircular canals (Figure 1a), and are responsible for detecting linear and angular acceleration. The range of stimulus frequencies detected by human hair cells varies considerably, from 0.1–20 Hz for vestibular organs to 20–20 000 Hz for the cochlea – in some mammals the upper boundary may extend beyond a dazzling 100 kHz. This is an extremely demanding task when considering that, for example, the encoded sound information (e.g. frequency, intensity and timing) has to be transmitted to the brain with high fidelity to be able to discriminate different sounds and localize them in space. Therefore, it is not surprising that impairment of hair cell function can lead to deafness and/or severe problems with postural control in humans.

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Figure 1. Morphological organization of the inner ear. (a) Different sensory structures of the inner ear. P.C., perilymphatic compartment and E.C., endolymphatic compartment. (b)–(d) Sensory neuroepithelia and accessory structures present in the semicircular canals (b), otolith organs (c) and the cochlea (d). Type I and II hair cells are found in the cristae and maculae; inner (IHCs) and outer (OHCs) hair cells are found in the organ of Corti. In the semicircular canals, the stereocilia are embedded in a gelatinous material called the cupula (b). Movement of the cupula, as a consequence of head rotation (white arrow), results in stereociliar deflection. In the saccule and utricle, the tips of the stereocilia are embedded in the otolith membrane (c), note the presence of several small pebbles called otoliths made of calcium carbonate and proteins. Otolith movement produced by vertical or horizontal head accelerations (white arrows) displaces the otolith membrane, which deflects the stereocilia. In the cochlea (d), sound-induced vibration of the basilar membrane causes a shear force between the tectorial membrane and the inner and outer hair cells, resulting in hair bundle displacement. For clarity, only one afferent or efferent fibre is shown to contact an IHC and OHC. This composite figure has been partially redrawn and reprinted with permission from Hennig Arzneimittel GmbH & Co. KG, Wiesbaden, Germany (www.hennig-arzneimittel.de).

The name hair cell derives from the highly specialized hair-like elements (stereocilia or hair bundle) that project from their apical surface. These hairs, with the only exception being the inner hair cells (IHCs: see later discussion), extend into special accessory structures present in the endolymphatic compartment (Figure 1a). These are the cupula in the semicircular canals (Figure 1b), the otolithic membrane in otolith organs (Figure 1c) and the tectorial membrane in the cochlea (Figure 1d).

The cochlea and the components of the vestibular apparatus are interconnected by fluid-filled tubes that form a labyrinth. The membranous labyrinth (purple: Figure 1a) is filled with endolymph, a solution rich in K+ ions and low in Na+ and Ca2+ (Pickles, 2008). The membranous labyrinth is separated from the bony labyrinth by the perilymph (light blue), which has an extracellular-like ionic composition. Hair cells and their nerve fibres are found in specialized neuroepithelial areas located within the fluid-filled tubes. In mammals, these regions are called the crista ampullaris (in the semicircular canals: Figure 1b), the otolithic macula (in the otolith organs: Figure 1c) and the organ of Corti (in the cochlea: Figure 1d). Tight junctions between the neck region of adjacent hair cells and supporting cells ensure that the endolymph bathing their apical surface does not mix with the perilymph bathing their basolateral region.

Two types of hair cells are present in the cochlea (Figure 1d), inner hair cells (IHCs) and outer hair cells (OHCs). OHCs are separated from IHCs by inner and outer pillar cells (supporting cells) which form the tunnel of Corti (Figure 1d). IHCs are supported by additional supporting cells called inner phalangeal cells. OHCs are mainly supported by the Deiter's cells. Within the spiral structure of the mammalian cochlea, hair cells are tonotopically organized such that their characteristic frequency (the frequency at which they respond best) gradually changes with position along the organ, with high-frequency cells located towards the base and low-frequency cells being located towards the apex. IHCs (∼3500 in humans) are the primary sensory receptors of the mammalian cochlea responsible for relaying acoustic information to the central nervous system via afferent auditory nerve fibres. OHCs act in parallel to enhance the sensitivity and frequency selectivity of the cochlea by active mechanical amplification (Brownell, 2006).

In the cristae and maculae of the vestibular end organs, hair cells are called Type I and Type II. Type I hair cells are only found in mammals, birds and some reptiles and are amphora or cylindrically shaped with a constricted neck (Figure 2). Type II hair cells are cylindrically shaped (Figure 2). Both Type I and Type II hair cells are surrounded by supporting cells, which have an irregular shape and microvilli protruding from their apical surface (Figure 2). Supporting cells within the cochlea and the vestibular apparatus are thought to be involved in generating/maintaining the different K+ concentrations present between the endolymph and perilymph. See also Auditory Processing, and Vestibular System

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Figure 2. Schematic diagram of the adult mammalian vestibular neuroepithelium. Two Type II hair cells (II), one Type I hair cell (I), three supporting cells (S.C.), afferent (Aff., red) and efferent (Eff., light blue) nerve fibres are shown. Type II hair cells are contacted by bouton terminals whereas the Type I cell's basolateral membrane is enveloped by the calyx terminal. Synaptic vesicles containing the neurotransmitter (glutamate) and the efferent neurotransmitter (acetylcholine) are also shown. Presynaptic vesicles in hair cells are shown tethered to the synaptic body (ribbon). For simplicity, only few afferent terminals are shown that face the presynaptic ribbons. The efferent synapse onto Type II hair cell is marked by a subsynaptic cistern (c.). An outer face (o.f.) synapse between the Type II hair cell and the calyx is also shown. The apical surface of hair cells is characterized by the hair bundle, whereas supporting cells have short microvilli. Only supporting cells contact the basement membrane. Below the basement membrane afferent nerve fibres become coated by the myelin sheath.

Hair Cell Innervation Patterns

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

IHCs are contacted by several afferent fibres that terminate in small rounded boutons. Afferent fibres are responsible for sending sound information transduced by the inner ear to the brain. Each afferent fibre innervates only one IHC (Pujol et al., 1998). In the mammalian cochlea, the activity of individual afferent neurons is driven by neurotransmitter released from specialized presynaptic structures named ribbon synapses (Fuchs, 2005; Sterling and Matthews, 2005). Each IHC is able to drive several afferent neurons. The heterogeneity of afferent sensitivity and response dynamics to a given sound frequency could be correlated to distinct synaptic properties within the same IHC (Meyer et al., 2009). Conversely, OHCs mainly receive efferent innervation, the role of which is to modulate the electromechanical amplification of the cochlear partition. The vestibular system is particularly rich in synaptic specializations (Figure 2), featuring bouton- and calyx-type afferent endings (Eatock and Lysakowski, 2006). In contrast to the cochlea, each vestibular afferent receives input from multiple ribbon synapses and connect to one or more hair cells (Goldberg, 2000). So-called bouton-type afferents receive synaptic inputs from several Type II hair cells. Calyx-type terminals receive synaptic inputs not only on their inner face from Type I hair cells (Figure 2), but also on their outer face from neighbouring Type II cells (Lysakowski and Goldberg, 2008). Dimorphic-type afferents contact both Type I and Type II hair cells. Efferent nerve terminals directly contact Type II hair cells or the calyx of Type I hair cells.

The hair cell afferent transmitter is glutamate and excites the afferent nerve terminal by binding to postsynaptic AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptors (Glowatzki et al., 2008). The efferent neurotransmitter acetylcholine, which mainly mediates an inhibitory response, can bind to metabotropic or ionotropic cholinergic receptors located in the hair cell's basolateral membrane or in the calyx (Figure 2). The role of the efferent vestibular innervation has yet to be assessed. See also Chemical Synapses, and Glutamatergic Synapses: Molecular Organisation

Hair Cell Stereocilia and Kinocilia

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

In the mammalian cochlea and vestibular apparatus the stereocilia are arranged in rows of increasing height (Figure 2; Furness and Hackney, 2006), like the pipes of a pipe organ. IHC stereocilia are arranged in about three slightly curved rows, with the tallest stereocilia facing the inner pillar cells. The stereocilia of OHCs are arranged in 3–6 rows in a V- or W-shaped pattern with the tallest stereocilia facing away from the pillar cells. The height of the stereocilia bundle increases from the base to the apex of the cochlea. At the tallest site of the bundle is a single kinocilium – cochlear hair cells lose their kinocilium during early stages of maturation. Similar to the cochlea, the stereocilia bundles of semicircular canal hair cells are organized such that the tallest stereocilia face the same direction. However, in the otolithic organs the tallest stereocilia are orientated in opposite directions on either side of a specialized region called the striola. The direction of stereocilia movement is morphologically and physiologically polarized (Furness and Hackney, 2006) – see next section.

Cochlear and vestibular hair cell stereocilia are approximately 0.1–0.2 μm in diameter. Vestibular hair cell stereocilia can be as much as 40 μm in length. Each stereocilium is composed of parallel actin filaments, cross-linked into rigid paracristalline arrays by the actin-bundling proteins fimbrin and espin, and ensheathed by a plasma membrane and glycocalyx. The kinocilium, a true cilium, consists of a thin bundle of fibrils made up of two central fibrils surrounded by nine double fibrils. The fibrils of the kinocilium end in the apical part of the hair cell in a bud-like swelling called the basal corpuscle.

Mechano-electrical Transduction

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

The biophysical process that converts incoming sound stimuli and head motion into an electrical signal in hair cells is known as mechano-electrical transduction. This process mainly occurs in the hair bundle of both auditory and vestibular hair cells. The bundle is extremely sensitive to mechanical stimuli; deflections in the order of a few nanometres are sufficient to initiate mechano-electrical transduction. All of the stereocilia (and kinocilium) in the bundle are joined along their lengths by axial filaments, which ensure that the bundle moves as a unit (Goodyear et al., 2005). Links extending from the tip of a shorter stereocilium to the lateral wall of its taller neighbour (tip links) play a central role in mechano-electrical transduction (Figure 2).

During sound stimulation or head movement, the mechanical displacement of the hair bundle towards its taller stereocilia (excitatory deflection) is likely to stretch the tip links that connect adjacent stereocilia (Pickles, 2008). The tension in the tip links is then transmitted to mechanically gated ion channels located at the tip of the stereocilia, resulting in their increased open probability and the flow of a cation current (mainly carried by K+ but also by Ca2+) from the endolymph into the cell (LeMasurier and Gillespie, 2005; Figure 3). This inward transducer current causes hair cells to depolarize and the consequent Ca2+-dependent release of neurotransmitter onto the afferent nerve terminals (see later). In the unstimulated hair cell, approximately 15% of the transducer channels are open. Therefore, deflection of the stereocilia in the inhibitory direction (towards the shorter stereocilia) closes these channels and hyperpolarizes the cell. Stereociliary deflection in directions other than in the plane of bilateral symmetry of the ciliary bundle (a plane from the shortest to tallest stereocilia) has little or no effect.

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Figure 3. Myosin-mediated mechano-transducer adaptation. In the absence of stimuli the stereocilia are in their resting position, where approximately 15% of the mechano-sensitive (MET) channels are open. For simplicity, only two stereocilia per bundle are shown. During an excitatory stimulus (gray arrow), stereocilia deflection produces an increase in tension of the rigid tip links, which pull down the MET channels. Sliding of the MET channel stretches a still unidentified elastic component (gating spring) connecting the MET channel and the myosin-1c protein. The interaction of the myosin-1c with the actin filaments inside the stereocilia is Ca2+/calmodulin-dependent. Stretching of the gating spring results in the opening of MET channels. The influx of Ca2+ ions into the stereocilia causes myosin-1c to slip down the actin cytoskeleton. This reduces tension at the gating spring and permits the MET channel closure (adaptation). As Ca2+ is removed by the stereocilia, mainly by Ca2+ pumps located in the stereocilia membrane (not shown), myosin-1c rebinds to the actin filament, although at a lower point. This interaction is able to exert sufficient tension on the gating spring to restore the normal (resting) sensitivity. At the end of the stimulus, while the hair bundle returns to its resting position, myosin-1c climbs along the actin filament to restore the normal sensitivity. This is a generally accepted model of adaptation, which is based on the assumption that the MET channels are located at the top of the tip link (e.g. on the taller stereocilia; for a review see: LeMasurier and Gillespie 2005. However, recent findings using fast Ca2+ imaging have shown that the MET channel is likely to be located at the bottom of the tip link (on the shorter stereocilia), questioning the above mechanism (Beurg et al., 2009).

Although the biophysical and morphological properties of the transduction apparatus have been extensively investigated (Fettiplace and Hackney, 2006; Furness and Hackney, 2006), its molecular identity remains elusive. The hair cells transducer channel shows no or very little homology with other known ion channels, although it has been suggested that it might be related to the transient receptor potential (TRP) family of nonspecific cation channels (Strassmaier and Gillespie, 2002). See also TRP Channels

An important feature of the transducer current is that it rapidly diminishes on maintained bundle deflection due to adaptation. The combination of two different mechanisms, both triggered by Ca2+ influx into the cell, underlies to adaptation: a slow adaptation (with a time constant of a few tens of millisecond) that is mediated by an unconventional myosin (myosin-1c: Figure 3) and a much faster adaptation (sub-millisecond in mammals) mediated by the direct action of Ca2+ on the transducer channel itself (Eatock, 2000; Fettiplace and Hackney, 2006). However, in the vestibular system it has been proposed that myosin-1c underlies both processes (Stauffer et al., 2005). The function of adaptation is to maintain the transducer channel within its most sensitive operational range following sustained bundle displacement to maximize its responsiveness, and to prevent saturation with larger stimuli.

Voltage-dependent Ion Channels

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

The receptor potential generated by the depolarizing inward transducer current is shaped by several types of voltage- and time-dependent ion channels located in the hair cell's basolateral region (Eatock and Hurley, 2003a, 2003b; Housley et al., 2006). In most hair cells a slow and a fast outward K+ current are present. The slow current is generally carried by a delayed rectifier potassium channel and the fast current by a ‘BK-type’ calcium-activated potassium channel. In most Type II vestibular hair cells a transient ‘A-type’ outward potassium current is also prominent around the resting membrane potential. Several inward currents are found in hair cells. These include a calcium current (L-type) and two inward rectifying K+ currents (IKir2.1 and Ih). Type I vestibular hair cells have a negatively activating K+ current, termed IKI (Correia and Lang, 1990) or IK,L (Rüsch and Eatock, 1996) that is not present in Type II vestibular hair cells. A similar negatively activating K+ current termed IK,n is present in mammalian cochlear OHCs and IHCs. However, the kinetics, pharmacology and ionic selectivity of IK,L and IK,n suggest that they are likely to be carried by different channels (Wong et al., 2004). The specific complement of ion channels expressed by hair cells located in different regions of a sensory epithelium change significantly, most likely to match distinct features of the complex natural stimulus such as different frequency and intensity components.

Ion channels in both auditory and vestibular hair cells are implicated in a variety of functional roles including: establishing the resting membrane potential; participating in the modulation of the hair cell's membrane potential; setting the hair cell's input impedance and thus determining its speed and sensitivity; filtering the membrane potential response; initiating the process of afferent fibres excitation (i.e. neurotransmitter release). See also Ion Channels, and Voltage-gated Potassium Channels

Calcium Channels and Neurotransmitter Release

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

The accurate transfer of sound and head movement information, encoded by the hair cell's receptor potential, to the afferent nerve fibres requires reliable synaptic transmission with high temporal precision. This is a remarkable task considering that even in the absence of stimulation, hair cell presynaptic active zones (the place where vesicle fusion occurs) can drive ‘spontaneous’ spiking activity in the afferent neuron at rates of up to or in some cases even beyond 100 Hz (Liberman, 1982). The afferent activity is mediated by the release of the neurotransmitter glutamate from hair cells (Glowatzki et al., 2008). In order for hair cells to achieve the speed and precision required to encode their physiological stimuli, especially for sound localization, each afferent nerve terminal receives information from a presynaptic specialization named the synaptic ribbon (Figure 2). Ribbon synapses are electron-dense organelles that tether a large number of synaptic vesicles at the cell's presynaptic active zones (up to 200 vesicles in mouse cochlear IHCs: Nouvian et al., 2006) and are found in sensory receptors that respond to sustained and graded stimuli such as those in the auditory, vestibular and visual systems (Sterling and Matthews, 2005). It is assumed that ribbons stabilize a large readily releasable pool of tens of vesicles, potentially by concentrating docked vesicles at the active zone. In contrast to conventional synapses, ribbon synapses are able to coordinate the synchronous fusion of several vesicles at one active zone. The full identity of the ribbon's molecular composition remains a major challenge. Current evidence indicates that ribbon synapses lack some of the more classical synaptic proteins such as synaptophysin and synapsin, which are found at conventional synapses (Jahn et al., 2003) and instead express other synaptic proteins such as Bassoon, Piccolo and Otoferlin (Nouvian et al., 2006). Calcium influx into hair cells is caused by the opening of CaV1.3 L-type Ca2+ channels, which represent the majority of the Ca2+ channels expressed in mammalian hair cells (Platzer et al., 2000). Because of the proximity (10–40 nm) of presynaptic Ca2+ channels to the putative Ca2+ sensor of exocytosis, the Ca2+ concentration can reach a high micromolar range which rises and falls within microseconds and allows a high temporal resolution of the signal (Moser et al., 2006).

Exocytosis at mature auditory IHC ribbon synapses has been shown to be highly Ca2+ efficient (requiring relatively little Ca2+ to trigger release), and in contrast to conventional synapses, is linearly dependent on Ca2+ entry over a physiological Ca2+ range (Johnson et al., 2005). This is likely to ensure that mature cells are capable of continuous vesicle release both spontaneously and in response to small and graded changes in membrane potential, allowing them to be suited for fine sound intensity discrimination over a wide dynamic range.

Very little is known about the coupling between the calcium current and exocytosis in mammalian vestibular hair cells; in lower vertebrates however, vesicle fusion is similarly triggered by Ca2+ entering through CaV1.3 L-type Ca2+ channels. See also Calcium and Neurotransmitter Release, Calcium Channels, and Synaptic Vesicle Fusion

Role of Outer Hair Cells in Signal Amplification

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

Although IHCs are responsible for relaying acoustic information to the central nervous system via afferent auditory nerve fibres, OHCs act in parallel to enhance the sensitivity and frequency selectivity of the cochlea by active mechanical amplification. Amplification occurs at a precise frequency, permitting the ear to discriminate sounds differing in frequency by less than 0.2% (1/240 of an octave). Consistent with their role as amplifiers, OHCs make a few or no synapses with afferent nerve fibres. Instead, they receive an extensive efferent input that regulates their mechanical activity. It is generally accepted that the mechanical amplification is generated via the voltage-dependent somatic electromotility of OHCs (Brownell et al., 1985). When an electrical pulse is applied to an isolated OHC, it moves along its long axis. OHCs contract when the cell is depolarized and elongate when the cell is hyperpolarized. The molecular motor for OHC electromotility is the voltage-sensitive membrane protein prestin (Zheng et al., 2000). Prestin appears to respond to changes in membrane potential by changing its cross-sectional profile in the membrane, generating large axial forces. However, it remains unclear how electromotility is able to operate at frequencies higher than a few kilo hertz where changes in the membrane potential are limited by the cell membrane time constant. Recent findings have shown that in mammals, Ca2+-driven active hair-bundle motility could also contribute to cochlear amplification (Chan and Hudspeth, 2005; Kennedy et al., 2005), similar to previous findings in non-mammals.

Development of the Cochlear and Vestibular Systems

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

The functional maturation of hair cells is an extremely ordered, complex process that must be completed before sound and head movement can be processed. It involves specific physiological and morphological changes of the auditory and vestibular apparatus. These changes occur over ‘critical periods’ of immature development (Housley et al., 2006).

Terminal mitosis is the last division a cell undergoes during development and marks the beginning of a permanent cell population. Hair cells of the mouse cochlea undergo terminal mitosis between embryonic day 12 and 15 (E12-E15: where the day of birth corresponds to about E20). Hair cell differentiation progresses in a basal to apical direction for several more days.

In the vestibular receptors, terminal mitosis in Type I and Type II hair cells occurs at E14 and E15, respectively, and their differentiation progresses from the striola towards the periphery (in otolith organs) or apex to the periphery (in the semicircular canal). At E16 vestibular immature hair cells with short stereocilia are evident and mechano-electrical transduction first appears (Géléoc et al., 2004). Synaptic contacts between hair cells and vestibular afferents usually occur after E18. Despite the similar onset of differentiation among hair cells, the maturation of mouse vestibular cells is completed before that of the cochlear cells (vestibular hair cells: at around birth; cochlear cells: >postnatal day 12, which in most rodents corresponds to the onset of hearing). During maturation, hair cells progressively acquire distinct voltage-dependent channels that turn immature cells into fully functional sensory receptors with properties tailored to their specific function and position within the sensory organ (Masetto et al., 2000; Housley et al., 2006). These biophysical changes occur simultaneously with the refinement of synaptic connections. In the cochlea, both the biophysical and morphological changes are thought to be driven by the spontaneous Ca2+-dependent action potential activity occurring in IHCs before the onset of hearing, similar to those observed in other parts of the nervous system (Moody and Bosma, 2005). In contrast to the cochlea, no spontaneous action potentials have been seen in immature vestibular hair cells, suggesting they use a different developmental strategy. See also Ear and Lateral Line of Vertebrates: Organisation and Development

Do Hair Cells Regenerate?

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

Hearing loss is a very common disorder affecting a few hundred million people worldwide (Brown et al., 2008). Although vestibular defects are less common, they can be very debilitating. Most types of deafness are caused by peripheral auditory defects that occur as a result of either structural (outer or middle ear) or sensory-neural (cochlear nerve and/or hair cell) abnormalities. Although many factors can cause hearing impairment (e.g. noise insult, ageing and aminoglycoside antibiotics) about half of the total number of hearing loss cases occurring in humans is attributed to genetic defects. When adult mammalian hair cells are damaged, their replacement is either very modest (vestibular organs) or absent (cochlea), and this is the reason why hearing loss and/or vestibular defects are irreversible processes in humans.

In contrast to mammals, hair cells in lower vertebrates (fish, amphibian and reptiles) and birds can regenerate spontaneously, following trauma or aminoglycoside-induced death, from the proliferation of neighbouring supporting cells or common progenitor cells (Goodyear et al., 2006). The newly formed hair cells exhibit biophysical properties and orientation appropriate for their position within the sensory neuroepithelium (Masetto and Correia, 1997). In adult mammals, supporting cell proliferation is very limited if any (Rubel et al., 1995), preventing sensory cell regeneration. Knowledge of how hair cell regeneration occurs in non-mammalian vertebrates is likely to be important for developing methods to stimulate hair cell regeneration in mammals. During recent years considerable effort has been made to understand, at the molecular level, the underlying mechanism that regulates cell fate during development and regeneration. Atonal homolog 1 (atoh1) (formerly known as math1 (mouse homolog of atonal 1)) gene expression promotes the differentiation of supporting cells into hair cells both during development and regeneration. atoh1 transcription is inhibited by the notch signalling pathway. The induced expression of atoh1 was sufficient to regenerate guinea-pig cochlear hair cells from the direct trans-differentiation of existing supporting cells (Izumikawa et al., 2005). Comparable results were obtained from mouse vestibular hair cells following aminoglycoside damage (Staecker et al., 2007). These results indicate that the potential exists for generating new functional hair cells in the adult mammalian cochlea and vestibule. These findings set the stage for the future development of inner ear gene therapy such as the expression of key developmental genes essential for the induction of hair cell regeneration (for recent reviews see Goodyear et al., 2006; Collado et al., 2008).

Acknowledgements

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

The Wellcome Trust, Deafness Research UK and The Royal Society (to WM: http://www.shef.ac.uk/bms/research/marcotti/) and the Ministero dell'Istruzione, dell'Università e della Ricerca (to SM), sponsored some of the work cited. WM is a Royal Society University Research Fellow and SM an Associate Professor at the University of Pavia.

End Notes
  1. Based in part on the previous version of this Encyclopedia of Life Sciences (ELS) article, Hair Cells by Manning J Correia.

Glossary
Adaptation

Sensory adaptation is a decrease over time in the responsiveness of the sensory system to a constant stimulus.

Afferent fibre

A nerve fibre that courses from the hair cells to the brain. The cell body of the afferent fibre is in Scarpa's (vestibular) or the spiral (auditory) peripheral ganglion.

Depolarization

Most excitable cells, including hair cells, have a negative resting potential (inside relative to outside). Depolarization refers to making the membrane potential less negative (more positive).

Efferent fibre

A nerve fibre that courses from the CNS to the hair cells and/or to the afferent terminal contacting the hair cell. The cell body of the efferent fibres is in the brainstem.

Exocytosis

The cellular secretion of macromolecules by the fusion of vesicles with the plasma membrane. Vesicle fusion is triggered by an increase in intracellular Ca2+ concentration.

Hyperpolarization

The opposite of depolarization, that is making the membrane potential more negative (less positive).

Ion channel

Ion channels are pore-forming integral proteins found in the lipid bilayer cell membrane. Ion channels help establish and control the small voltage and ion concentration gradient across the plasma membrane of all living cells (see receptor potential) by allowing the flow of ions down their electrochemical gradient. They may be highly selective for a single ion, that is potassium or calcium channels.

Notch

The Notch receptor is a membrane spanning protein, with part of it inside and part outside the cell. Ligand proteins binding to the extracellular domain induce proteolytic cleavage and release of the intracellular domain, which enters the cell nucleus to alter gene expression. Because most ligands are also transmembrane proteins, the receptor is normally triggered only from direct cell-to-cell contact. Jagged and Delta are Notch ligands expressed by inner ear supporting cells.

Receptor potential

The change in transmembrane potential caused by a sensory stimulus. The receptor potential varies proportionally to the stimulus intensity. The intensity of the receptor potential determines the frequency of action potentials travelling to the nervous system.

Transcription factor

A transcription factor is a protein that binds to specific DNA sequences and thereby controls the transfer (or transcription) of genetic information from DNA to RNA either positively or negatively.

References

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading

Further Reading

  1. Top of page
  2. Introduction: The Inner Ear and Their Sensory Receptors
  3. Hair Cell Innervation Patterns
  4. Hair Cell Stereocilia and Kinocilia
  5. Mechano-electrical Transduction
  6. Voltage-dependent Ion Channels
  7. Calcium Channels and Neurotransmitter Release
  8. Role of Outer Hair Cells in Signal Amplification
  9. Development of the Cochlear and Vestibular Systems
  10. Do Hair Cells Regenerate?
  11. Acknowledgements
  12. References
  13. Further Reading
  • Eatock RA, Fay RR and Popper AN (2006) Vertebrate Hair Cells. New York: Springer.
  • Goldberg JM and Fernández C (1984) The vestibular system. Handbook of Physiology. The Nervous System, pp. 8771022. Bethesda: American Physiological Society.
  • Harada Y (1988) The Vestibular Organs – S.E.M. Atlas of the Inner Ear. Amsterdam: Kugler & Ghedini Publications.
  • Salvi RJ, Popper AN and Fay RR (2008) Hair Cell Regeneration, Repair, and Protection. New York: Springer.
  • Wilson VJ and Melvill Jones G (1979) Mammalian Vestibular Physiology. New York: Plenum Press.