Nitric oxide--a versatile key player in cochlear function and hearing disorders

Nitric oxide (NO) is a signaling molecule which can generally be formed by three nitric oxide synthases (NOS). Two of them, the endothelial nitric oxide synthase (eNOS) and the neural nitric oxide synthase (nNOS), are calcium/calmodulin-dependent and constitutively expressed in many cell types. Both isoforms are found in the vertebrate cochlea. The inducible nitric oxide synthase (iNOS) is independent of calcium and normally not detectable in the un-stimulated cochlea. In the inner ear, as in other tissues, NO was identified as a multitask molecule involved in various processes such as neurotransmission and neuromodulation. In addition, increasing evidence demonstrates that the NO-dependent processes of cell protection or, alternatively, cell destruction seem to depend, among other things, on changes in the local cochlear NO-concentration. These alterations can occur at the cellular level or within a distinct cell population both leading to an NO-imbalance within the hearing organ. This dysfunction can result in hearing loss or even in deafness. In cases of cochlear malfunction, regulatory systems such as the gap junction system, the blood vessels or the synaptic region might be affected temporarily or permanently by an altered NO-level. This review discusses potential cellular mechanisms how NO might contribute to different forms of hearing disorders. Approaches of NO-reduction are evaluated and the transfer of results obtained from experimental animal models to human medication is discussed.     

Possible Ca2+-dependent mechanism of apical outer hair cell modulation within the cochlea of the guinea pig

Calcium ions were precipitated with potassium antimonate after injection of the inorganic calcium channel blocker MnCl₂ or the inorganic potassium channel blockers BaCl₂ or CsCl into the perilymph of the scala vestibuli of the guinea pig. The spatial distribution of the formed histochemical reaction products within the organ of Corti was studied by energy-filtering transmission-electron microscopy. Compared with untreated control ears, the number of the formed precipitates drastically increased at the extracellular side of the lamina reticularis after application of the various inorganic channel blockers. The apical side of the outer hair cells and the intervening Deiter cells were covered by a thick layer of calcium precipitates, whereas the number of histochemical reaction products was clearly reduced in the nearby acellular tectorial membrane. The high calcium content within the formed reaction products at the lamina reticularis could be demonstrated by elemental mapping and by electron energy-loss spectroscopy. To ascertain the alterations in the amounts of the calcium precipitates within the tectorial membrane after application of the various inorganic channel blockers, the precipitate densities were determined semiquantitatively by an image processing system and the values obtained compared with those of untreated control specimens. The observed histochemical results are in good agreement with published electrophysiological findings concerning the spatial distribution of ion channels located at the apical outer hair cell membrane. The detected alterations in the spatial distribution of calcium precipitates might correspond to calcium-dependent processes involved in outer hair cell modulation. Received: 4 November 1996 / Accepted: 28 October 1997