**4. Inner and outer hair cells – the mechanoelectrical transducers**

#### **4.1. Stereocilia**

The stereocilia of the inner ear hair cells are microvilli-derived and unique cell structures that represent the gate for stimulus detection and correlate anatomically with distinct cochlear functions, including mechanoelectrical transduction, cochlear amplification, adaptation, frequency selectivity and tuning [27]. The stereocilia have a typical staircase arrangement connected with lateral and tip links stabilizing the mature hair-bundle structure. The number of stereocilia on each hair cell decreases in a linear fashion with distance from the base of the cochlea. However, stereociliary length increases as a hyperbolic function of distance along the cochlear duct [28]. Contrastingly, in the vestibular organs one kinocilium is bound to the tallest of 50–80 stereocilia, arranged in a distinct geometrical alignment [29]. Differences in ciliary gradation also exist between the three rows of stereocilia on outer hair cells and the two rows on inner hair cells, with the tallest row positioned laterally [30]. The longest stereocilia layer left imprints on the undersurface of the tectorial membrane at the region known as Hardesty's or Kimura's membrane [31]. The stereocilia of the inner hair cells do not have the same firm attachment to the tectorial membrane as the stereocilia of the outer hair cells suggesting different modes of mechanical coupling between the tectorial membrane and the inner and outer hair cell stereocilia [30].

The term stereocilia does not reflect their origin, as these microvilli-derived structures should be clearly distinguished from microtubule-based, true cilia. Stereocilia are constructed of crosslinked actin filaments in a parallel, paracrystalline array, giving stereocilia their stiffness, are rich in fimbrin and their stereociliary rootlets contain actin and tropomyosin [32]. The actin filaments insert with an electron-dense rootlet into a fibrous-anchoring structure, the cuticular plate. The cuticular plate is a network of actin filaments, which also contain myosin, α-actinin, fimbrin, tropomyosin, fodrin and calcium-binding proteins [33, 34].

When sound is induced, fluids move through the cochlear duct and vibrate the basilar membrane with the sensory hair cells against the tectorial membrane, which leads to deflection of the stereocilia and activation of the mechanoelectrical transduction channels gated by the tip links. They are extracellular, cell surface associated, fine filaments, gating the mechanotransducer channel by deflecting the hair cell bundle towards the taller row, depolarizing the hair cells and enabling potassium influx. A deflection in the opposite direction leads to hyperpolarization [35].

The stereocilia, together with the structures of the hair cell body, probably contribute actively and/or passively to cochlear amplification. They also influence the amplification properties of the outer hair cell body enabled by bending leading to a membrane potential change in outer hair cells and causing length changes [36]. These length changes feed force back to the basilar membrane on a cycle-by-cycle basis and so tune its otherwise shallow vibrations to the characteristic frequency [37]. At low frequencies, the stereociliary sensitivity is proportional to the cube of the heights of their hair bundles, whereas at high frequencies the sensitivity is proportional to the inverse of their heights [38]. Frequency and stiffness are proportional to each other [39] correlating with the height of the stereocilia [40]. The cochlear amplifier gain is the difference between the peaks in the sensitivity functions for low- and high-intensity tones [41].

#### **4.2. Inner hair cells**

**Figure 3.** Schematic representation of a cochlear turn with the most significant recycling pathways of K+

**4. Inner and outer hair cells – the mechanoelectrical transducers**

The stereocilia of the inner ear hair cells are microvilli-derived and unique cell structures that represent the gate for stimulus detection and correlate anatomically with distinct cochlear functions, including mechanoelectrical transduction, cochlear amplification, adaptation,

served).

**3.3. Supporting cells**

212 Advances in Clinical Audiology

**4.1. Stereocilia**

more, it depicts the organ of Corti composed of sensory inner (IHC) and outer (OHC) hair cells and supporting cells. Inner pillar cells (IPC), outer pillar cells (OPC), Deiters cells (DC), Hensen cells (HC), Claudius cells (CC), external or outer sulcus cells (ESC), internal or inner sulcus cells (ISC), spiral limbus (Li), interdental cells (IDC), Reissner's membrane (RM) and stria vascularis (StV) adjacent to the fibrous spiral ligament (SL) (with permission from Professor G. van Camp, University of Antwerp, Belgium modified by Ref. [77]. Copyright © 2004, Springer-Verlag. All rights re-

The organ of Corti encloses the outer hair cells and the inner hair cells, which are stabilized by inner sulcus and inner and outer pillar cells. The outer hair cells are placed on top of one Deiters cell each. Besides, the organ of Corti encloses two small endolymph spaces, the Nuel space and the outer tunnel, and one perilymph space, the inner tunnel. The inner sulcus cells and the interdental cells terminate the organ of Corti into the spiral limbus and the tectorial membrane. The outer sulcus cells connect to the stria vascularis and spiral ligament (**Figure 3**). The secretory stria vascularis, the vestibular dark cells and endolymphatic sac and the nonsecretory vestibular transitional cells, the Reissner's membrane, the sulcus cells, the spiral limbus cells, the Deiters cells and the lateral or outer supporting cells (Hensen and Claudius cells) are responsible for fine regulation of inner ear fluids including the maintenance of ion and osmolarity gradients and potassium recirculation. The lateral or outer supporting cells are located between the outer hair cells and outer sulcus cells. The necessity for precise fine regulation of the endolymph is underlined by the fact that basally to the Hensen cells, Boettcher cells and medioapically to the Hensen cells cover or tectal cells were distinguished [26].

ions. Further-

The tip links of the stereocilia of the inner hair cells are the location for the mechanoelectrical transduction of the cochlea, long searched for. There exist about 3500 inner hair cells that are grouped in one row, in contrast to about 12000 outer hair cells that are grouped in three rows. 90–95 % of all innervation supplies the inner hair cells and each inner hair cell has contact with about fifteen to twenty neurons, of which about 90 % are afferent neurons [42, 43].

Inner hair cells show a characteristic 'flask' shape, displaying a constriction in the neck region. Relative to the surface of the organ of Corti, the cell body is angled towards the centre of the cochlear spiral (the modiolus) and away from the supporting pillar cell. The apical half of the cell contains the nucleus, and the infranuclear region shows an extensive and seemingly continuous network of intracellular endoplasmic reticulum membranes, associated with mitochondria and cytoplasmic vesicles. The afferent nerve endings form characteristical ribbon synapses around the entire baso-lateral region below the level of the nucleus [42]. Ribbon synapses are specialized for the precision and speed required to process auditory information and show tonotopical variation in function and form along the cochlear duct [44].

The inner hair cells are embedded for stabilization between inner sulcus cells and inner pillar cells, which shape the stiffness and elastic reactance of the travelling wave-processing structures [45]. Already, the basilar membrane and the inner and outer hair cells with their receptor potentials show tuning characteristics similar to the characteristical tuning of the cochlear afferent neurons [46].

#### **4.3. Outer hair cells**

The inner ear is not just a mechanoreceptor, but is capable to an active processing by the outer hair cells. The active component can be up to more than 100 times larger than the classical basilar membrane vibration. The outer hair cells enhance and focus the amplitude of the travelling wave by its contractions at sound pressure levels up to 60 dB (cochlear amplification) [47]. But the outer hair cells with their W-pattern-aligned stereocilia are not just a cochlear amplifier; they are three-dimensionally regulators for bone conduction and the natural exposition to bone vibrations.

To process the sound waves three-dimensionally, the outer hair cells are positioned on Deiters cells. Corresponding to the necessity for continous fast and active response to stimulation, they are surrounded by two endolymph spaces, the outer tunnel and the Nuel space.

The outer hair cells with their micromechanical properties enhance frequency selectivity and the tone intensity range. Stimulus protection, distance adjustment and sharpness enhancement in the eye are executed by the micromechanical light accommodation of the lens and the pupils and the biochemical and electrophysiological light accommodation by variation of the amount of photopigment and the open probability of transduction channels by the photoreceptors.

Hyperpolarization mediated by specific GABAA receptors (gamma aminobutyric acid A) causes expansion of prestin molecules, which elongates the outer hair cell [48]. Stimulation of ACh receptors (acetylcholine) leads to opposite outer hair cell changes [49]. Those outer hair cell changes can be measured as otoacoustic emissions (OAEs, spontaneous and evoked).

Contrastingly to the innervation of inner hair cells, the afferent nerve-receptor cell ratio is with about 1:10 negative [43, 50].
