Suzanne de Bruijn

23 General introduction The cochlear chambers are separated from each other by the Reissner’s membrane and thebasilarmembranewhichareessential formaintenanceof theendocochlear potential. The scala media is filled with endolymph fluid (potassium rich), the scala tympani and vestibuli are filled with perilymph fluid (sodium rich). The stria vascularis, that is part of the lateral wall of the cochlear duct, is responsible for the secretion of a constant flow of potassium ions into the endolymph and maintaining its ion homeostasis. The scala vestibuli and scala tympani are joined via an opening (helicotrema) positioned at the apical end of these compartments, allowing their fluids to mix. The oval window is located at the basal part of the scala vestibuli (upper chamber), the round window is located at the basal part of the scala tympani. 25 The organ of Corti is the sensory epithelium of the inner ear and resides within the scala media ( Figure 3C ). The epithelium consists of one row of inner hair cells and three rows of outer hair cells which are separated by supporting cells. The hair cells function as sensory receptors; the outer hair cells enhance sound sensitivity and selectivity whereas inner hair cells are responsible for signal transmission to the afferent nerve terminals of the cochlear nerve. 26 Actin-rich structures protrude from the apical surface of the hair cells: the stereocilia. These are anchored in the cuticular plate. Stereocilia are organized in a V-shape staircase-like pattern and are connected by horizontal links and tip-links. 27,28 The kinocilium is the only true microtubule-based primary cilium and located lateral to the row of largest stereocilia. The kinocilium elongates and determines the orientation of the hair bundle during development, and disappears in mammals before or shortly after birth depending on the species. 28-30 The different types of supporting cells that are present in the organ of Corti have a pivotal role in the development of the sensory epithelium and preserve its structural integrity and homeostasis. 29 Sensory hair cells are located between the basilar membrane and the tectorial membrane in the cochlea. Sound-evoked fluid movements trigger vertical (basilar membrane) or horizontal (tectorial membrane) displacement of these membranes. The combination of movements results in bending of the stereocilia. The displacement induces the opening of cation-selective mechanotransduction channels located at the lower end of tip links, allowing influx or efflux of potassium ions from the endolymph. Depending on the bending direction of the stereocilia, the hair cell will depolarize or hyperpolarize. As a result, voltage-gated calcium channels will open in the cell soma, allowing calcium-dependent neurotransmitter release at the synapses of the hair cells. An action potential is generated within the auditory nerve and a stimulus will be transmitted to the auditory cortex in the brain. 25 Upon repolarization of the hair cell, ion