**3. Supporting structures**

geometrically arranged finger-like processes, the stereocilia, are the mechanoelectrical transducers of the mechanoreceptor organ ear. The complex afferent and efferent innervation of the hair cells respond to further fine processing of the hearing stimulus. In this context, the efferent innervation supplies further qualities, in particular noise protection, mediation of selective attention and improvement of signal-to-noise ratio. It also supports adaptation and frequency selectivity by modification of the micromechanical properties of the outer hair cells. The past five decades of molecular biological research involved immense achievements in understanding of the physiological and biochemical mechanisms leading to current genetic-

The human cochlea consists of about two and a half turns and is about 9 cm in length from the oval window to the helicotrema, corresponding to a frequency gradient starting with high

The middle ear main function is to achieve mechanical gain by the ossicles as a lever and the tympanic membrane and oval window as a plane focuser. Besides, the middle ear makes the stimulus processable by harmonizing the sound wave resistance (impedance) of air and

Adaptation mechanisms are characteristical for a sense organ, and as the cochlea has to process travelling waves continuously, it involves all molecular structures and biochemical processes of the inner ear. Adaptation lowers the system requirements, protects from overstimulation and reflects the environmental necessities of stimulus perception. In addition, it characterizes tone and music perception. Contrastingly, to the chemical receptors of the olfactory and gustatory system and the dermal mechano-, and thermoreceptors, sound adaptation does not lead to no stimulus perception at all. Generally speaking, the adaptation time constant is faster in hair cells at the high-frequency end than at the low-frequency end, what probably contrib-

Different adaptation mechanisms contribute to inner ear function, namely voltage-dependent hair-cell properties, structural hair-bundle characteristics and afferent transmitter release. Fast adaptation operates around the most sensitive portion of the hair cell activation, whereas larger displacements of the hair bundle induce slow adaptation [4]. Fast adaptation has been identified in both cochlear and vestibular hair cells, but is the main form of adaptation in cochlear hair cells. Slow adaptation has been identified in all but mammalian auditory hair cells, and is the predominant adaptation mechanism found in vestibular hair cells [5–7]. (Comparison of the adaptation mechanisms of the human sense organs and receptor cells is described at the end of the article in **Table 1**. Comparison of the perception qualities of the human sense organs and further comparison are listed in **Table 2**. Comparison of the structural

based, nanotechnology-based and stem cell research [1, 2].

perilymph and the hair cells, respectively (**Figure 1**).

frequencies at the base and proceeding to low frequencies at the apex.

**2. Hearing system qualities**

208 Advances in Clinical Audiology

utes to frequency selectivity [3].

characteristics of the human sense organs.)

#### **3.1. Communication routes of the inner ear filled with endo- or perilymph**

The cochlea consists of three scalae that contain endo- and perilymph. The scala media contain endolymph, where osmotic and ionic characteristics are close to the intracellular hair cell milieu (high potassium content, K+ = 144 mval/l), and the scala tympani and vestibuli contain perilymph, which can be compared to cerebrospinal fluid (high sodium content, Na+ = 140 mval/l). There exist three communication routes between the intracranial spaces and the inner ear, the vestibular aqueduct, the cochlear aqueduct and the internal auditory canal [8]. The vestibular aqueduct contains the endolymphatic duct that begins with the union of the utricular and saccular ducts and ends in a blind pouch, the endolymphatic sac, which is embedded between two dural blades, located in the epidural space and shows immunological competence. The cochlear aqueduct contains the perilymphatic or periotic duct and possesses communication with the subarachnoidal space (**Figure 2**).

The aqueducts provide functionality for continuous response to stimulation to both inner ear sense systems, the cochlea and the vestibular organs, maculae of the utricle and saccule and cupulae of the three semicircular canals, by pressure equilibrium, participate in inner ear fluid regulation, make longitudinal flow feasible and thus possess a key role in guaranteeing adequate response to stimulation. Pressure equilibrium is primarily the function of the cochlear aqueduct, whereas fluid circulation is dependent on an intact vestibular aqueduct, but various interactions exist.

The main drainage of the inner ear is maintained by two to four veins of the cochlear aqueduct, and to a lesser extent by one or more, usually two at the proximal termination-located vessels of the vestibular aqueduct [9–11]. The protein and ionic composition, the endolymphatic potential and resting potential of the hair cells show differences in the distinct parts of the endolymphatic fluid spaces. These gradients and the fluid circulation are essential for adequate response to stimulation. Procedures which expand the endolymphatic space induce endolymph flow towards the base of the cochlea, contributing to the removal of electrolytes and volume. Procedures which reduce cochlear endolymph volume lead to apically directed flow in the cochlea, contributing to the addition of electrolytes and volume [12].

**Figure 2.** Schematic presentation of the labyrinth and aqueducts. AC: cochlear aqueduct; DE: endolymphatic duct; SE: endolymphatic sac; U: utricle; S: saccule; SS: sigmoid sinus; MAI: internal acoustic meatus. The white area represents the perilymphatic space; within it is the endolymphatic space in black. The endolymphatic duct is contained in the vestibular aqueduct; the perilymphatic or periotic duct is contained in the vestibular aqueduct; the endolymphatic sac protrudes from the vestibular aqueduct aperture protected by a bony operculum (op) and spreads out into the epidural space (with permission from Ref. [76]. Copyright © 2004, Springer-Verlag. All rights reserved).

#### **3.2. Stria vascularis**

The regulation of inner ear fluid homeostasis, with its parameters volume, concentration, osmolarity and pressure, is the basis for adequate response to stimulation [13]. The ion and water transport in the inner ear help maintain the proper potassium concentration required for hair cell function. Potassium is the major charge carrier for sensory transduction. It is ideal for this role, since it is by far the most abundant ion in the cytosol and responsible for the large endocochlear potential of 80 mV which is the driving force for mechanoelectrical transduction. Contrastingly, the endovestibular potential in the semicircular canals is ±1 mV [14].

competence. The cochlear aqueduct contains the perilymphatic or periotic duct and possesses

The aqueducts provide functionality for continuous response to stimulation to both inner ear sense systems, the cochlea and the vestibular organs, maculae of the utricle and saccule and cupulae of the three semicircular canals, by pressure equilibrium, participate in inner ear fluid regulation, make longitudinal flow feasible and thus possess a key role in guaranteeing adequate response to stimulation. Pressure equilibrium is primarily the function of the cochlear aqueduct, whereas fluid circulation is dependent on an intact vestibular aqueduct,

The main drainage of the inner ear is maintained by two to four veins of the cochlear aqueduct, and to a lesser extent by one or more, usually two at the proximal termination-located vessels of the vestibular aqueduct [9–11]. The protein and ionic composition, the endolymphatic potential and resting potential of the hair cells show differences in the distinct parts of the endolymphatic fluid spaces. These gradients and the fluid circulation are essential for adequate response to stimulation. Procedures which expand the endolymphatic space induce endolymph flow towards the base of the cochlea, contributing to the removal of electrolytes and volume. Procedures which reduce cochlear endolymph volume lead to apically directed flow

**Figure 2.** Schematic presentation of the labyrinth and aqueducts. AC: cochlear aqueduct; DE: endolymphatic duct; SE: endolymphatic sac; U: utricle; S: saccule; SS: sigmoid sinus; MAI: internal acoustic meatus. The white area represents the perilymphatic space; within it is the endolymphatic space in black. The endolymphatic duct is contained in the vestibular aqueduct; the perilymphatic or periotic duct is contained in the vestibular aqueduct; the endolymphatic sac protrudes from the vestibular aqueduct aperture protected by a bony operculum (op) and spreads out into the epidur-

The regulation of inner ear fluid homeostasis, with its parameters volume, concentration, osmolarity and pressure, is the basis for adequate response to stimulation [13]. The ion and water transport in the inner ear help maintain the proper potassium concentration required

al space (with permission from Ref. [76]. Copyright © 2004, Springer-Verlag. All rights reserved).

in the cochlea, contributing to the addition of electrolytes and volume [12].

communication with the subarachnoidal space (**Figure 2**).

but various interactions exist.

210 Advances in Clinical Audiology

**3.2. Stria vascularis**

The stria vascularis, located at the lateral wall of the cochlear duct, is the main structure responsible for endolymph secretion of the cochlea. It is connected to the spiral prominence, to Reissner's membrane and to the spiral ligament, which binds to the otic capsule. The stria vascularis represents one of the few epithelial types that contain capillaries. The stria vascularis has a higher oxygen consumption than brain tissue, and the strial capillaries are larger in diameter, with a higher haematocrit and a slower flow than the capillaries of any other tissue type [15]. The strial marginal cells show structural characteristics for fluid transport. They possess extensively infolded basolateral membranes with mitochondria providing the energy for active transport mechanisms, and microvilli located at the apical and basal sides increasing surface area. The stria vascularis consists of three cell layers: marginal cells, intermediate cells and basal cells. The intermediate cells, with their extensive, active transport mechanisms, are responsible for generating the endolymphatic potential. Consequently, the marginal cells possess a positive intracellular potential similar to that of the scala media [16].

A distinct pattern of tight and gap junctions, barrier and transport proteins maintains endolymph composition and generates endolymphatic potential, facilitating sensory transduction and reflecting fine regulation and a wide range of responses to stimulation. The transport proteins are regulated by purinergic, adrenergic and muscarinic receptors, steroids, vasopressin and atrial natriuretic peptide (ANP). There is evidence that the stress hormones noradrenaline and adrenaline, corticosteroids and mineralocorticosteroids possess a key role in inner ear homeostasis and sensory transduction. Besides, there exists a strongly expressed and largely non-overlapping distribution pattern for the different aquaporin (AQP) water channel subtypes in the inner ear, suggesting the existence of regional, subtype-specific water transport pathways [17–19]. The regulation of water transport in the inner ear probably requires concerted actions of multiple types of AQPs [20].

According to the tonotopy of the cochlea, potassium concentration and circulation are generally stronger at the cochlear base, and these gradients are maintained by extensive potassium recirculation cycles (**Figure 3**). In the auditory system, potassium circulation begins with the entrance of potassium into the sensory cells via the apical transduction channel. After entering the inner and outer hair cells, potassium recirculates mainly by a medial and a lateral pathway, and further smaller pathways through Reissner's membrane and the outer sulcus cells [21–23]. The medial pathway from the inner hair cells and the inner radial nerves involves inner sulcus cells, limbal fibrocytes and interdental cells. The lateral pathway from the outer hair cells consists of potassium delivery into the perilymph, absorption by the spiral ligament cells and entrance into the stria vascularis via strial intermediate cells [24, 25].

**Figure 3.** Schematic representation of a cochlear turn with the most significant recycling pathways of K+ ions. Furthermore, 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 reserved).

#### **3.3. Supporting cells**

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].
