17 Cell Death in the Inner Ear

The inner ear transduces sound energy and head motion into neural impulses. These signals are detected by six sensory patches in the fluid-filled spaces of the inner ear. The snail-shaped cochlea detects sound, whereas the vestibular system serves balance and gravity-detection functions. All six sensory patches in the inner ear use mechanosensory hair cells to transduce fluid motion signals into neurotransmitter release. These sensory cells are sensitive to death from noise trauma, aging, and certain therapeutic drugs. Hair cells in nonmammalian vertebrates are regenerated after they die, resulting in functional recovery of hearing and balance. In contrast, mammalian sensory hair cells are not regenerated, and their loss results in permanent hearing and/or balance disorders. Cochlear hair cells make synaptic connections with spiral ganglion neurons. Spiral ganglion neurons are bipolar cells with dendrites that synapse with the basal surfaces of hair cells and axons that comprise the eighth cranial nerve. Hair cells provide trophic support to spiral ganglion neurons. Therefore, death of hair cells is often followed by spiral ganglion neuron degeneration. Hearing loss is the most common sensory impairment in humans and is the sixth most common chronic health problem in the United States. This chapter addresses apoptotic death of sensory hair cells in response to ototoxic drugs and the subsequent death of spiral ganglion neurons (SGNs).

1. HAIR CELLS ARE THE SENSORY RECEPTOR CELLS IN THE

HEARING AND BALANCE ORGANS OF THE INNER EAR

The mechanosensory hair cell is a polarized cell characterized by a bundle of rigid stereocilia embedded in the apical surface. These stereocilia project into the fluid of the endolymphatic compartment. Endolymph is a unique extracellular fluid that is high in potassium,

which is secreted into the endolymphatic space by the stria vascularis. When sound waves travel through the ear canal and into the middle ear space, the three bones of the ossicular chain transmit this airborne energy into fluid motion in the inner ear (Figure 17-1). The fluid motion results in deflection of the stereocilia bundles on the apical surfaces of hair cells in the cochlear organ of Corti. This deflection opens mechanically gated ion channels in the stereocilia and allows cations (primarily K+ and Ca2+ ) from endolymph to enter the hair cell. The influx of cations results in a receptor potential that causes opening of voltage-gated Ca2+ channels, triggering the release of glutamate from the basal surface of the inner hair cell. The neurotransmitter enters the synaptic cleft and activates receptors on afferent projections of spiral ganglion neurons. In the vestibular system, the three semicircular canals are oriented at right angles to one another and serve to detect angular acceleration of the head. Each semicircular canal contains a sensory epithelium called the crista ampullaris, which contains hair cells that are activated by the movement of fluid in the semicircular canals as the head moves. This allows for detection of angular head movement in three dimensions. The vestibule of the ear is between the semicircular canals and the cochlea, and it contains the maculae of the utricle and saccule, which are oriented at right angles to one another. The utricle detects linear acceleration, whereas the saccule detects gravity. The utricle and saccule are both otolithic organs, meaning that the stereocilia are coupled to a mass (called otoconia). When the otoconia move in relation to the hair cells, the stereocilia are deflected and the cell releases neurotransmitter. Together, these six organs (the organ of Corti, utricle, saccule, and three semicircular canals) comprise the sensory receptor portions of the inner ear (Figure 17-1).