Phantom auditory perception (tinnitus): mechanisms of generation and perception

The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from the alveolar region in a series of temporal phases. The earliest, lasting several weeks, appears to include the clearance of phagocytosed particles via the bronchial tree. The terminal phases appear to be related to solubility at interstitial sites. While the mechanisms and dynamics of particle deposition and clearance are reasonably well established in broad outline, reliable quantitative data are lacking in many specific areas. More information is needed on: (1) normal behaviour, (2) the extent of the reserve capacity of the system to cope with occupational exposures, and (3) the role of compensatory changes in airway sizes and in secretory and transport rates in providing protection against occupational exposures, and in relation to the development and progression of dysfunction and disease.

https://oem.bmj.com/content/oemed/37/4/337.full.pdf

Deposition, retention, and clearance of inhaled particles

Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease.

The exquisite sensitivity of the cochlea, which mediates the transduction of sound waves into nerve impulses, depends on the endocochlear potential and requires a highly specialized environment that enables and sustains sensory function. Disturbance of cochlear homeostasis is the cause of many forms of hearing loss including the most frequently occurring syndromic and non-syndromic forms of hereditary hearing loss, Pendred syndrome and Cx26-related deafness. The occurrence of these and other monogenetic disorders illustrates that cochlear fluid homeostasis and the generation of the endocochlear potential are poorly secured by functional redundancy. This review summarizes the most prominent aspects of cochlear fluid homeostasis. It covers cochlear fluid composition, the generation of the endocochlear potential, K+ secretion and cycling and its regulation, the role of gap junctions, mechanisms of acid–base homeostasis, and Ca2+ transport.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2006.112888

Supporting sensory transduction: cochlear fluid homeostasis and the endocochlear potential

The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main clinical presentations: myopathic (OMIM 609560) and hepatocerebral1 (OMIM 251880). Known mutant genes, including TK2 (ref. 2), SUCLA2 (ref. 3), DGUOK (ref. 4) and POLG5,6, account for only a fraction of MDDS cases7. We found a new locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on this locus using a new integrative genomics strategy. One of the top-scoring candidates was the human ortholog of the mouse kidney disease gene Mpv17 (ref. 8). We found disease-segregating mutations in three families with hepatocerebral MDDS and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product9, MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and mtDNA depletion, not only in affected individuals but also in Mpv17−/− mice.

MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion

The presence of melanin in the inner ear was established more than a century ago, but the exact biological function of the pigment in the labyrinth has yet to be determined. In this brief review, the correlation of pigmentation and inner ear function, as well as the presumed role of melanocytes in hereditary diseases are discussed. Special attention was drawn to the composition of melanin and its presumed function as a biological reservoir for divalent ions and as an ion exchanger, as well as an intracellular buffering system for calcium. It is pointed out that melanin is capable of binding ototoxic drugs. Finally, morphological responses of melanocytes to local disturbance of Ca++ homeostasis in the inner ear are described as 1) intracellular movement and intraepithelial deposition of melanosomes; 2) cell motility; 3) neomelanogenesis; and 4) enhanced exocytotoxic/endocytotic activity. The possible consequences of this malfunction of the melanocytes on the inner ear function are discussed.

Physiology and Pathophysiology of Inner Ear Melanin

We found changes in Ca++ activity and DC potential during the development of experimentally induced endolymphatic hydrops in guinea pigs. These findings indicate that there is some correlation between Ca++ activity and DC potential in the cochlear endolymph.

Changes in Ca++ activity and DC potential in experimentally induced endolymphatic hydrops.

We measured Ca++ activity in the different parts of the endolymphatic space by using a doublebarrelled electrode with calcium liquid ionic exchanger. In the region of the endolymphatic sac, Ca++ activity (4.7×10−4
M) was much higher than in the cochlear duct (2.7×10−5
M) and semicircular canal (2.6×10−4
M). These findings suggest that Ca++ may also have a significant role in abnormal states.

Ca++ activity in the endolymphatic space

An imbalanced Ca++-homeostasis in the inner ear was demonstrated using an animal model for Meniere's disease (MD). An increase of Ca++ concentration in the endolymph, as well as in some cells of the inner ear tissue, causes a rise of osmotic pressure and decrease of electric potential. Based on these results, we assume a new aspect in the pathophysiology of MD. It is proposed that the common denominator of MD, experimental endolymphatic hydrops (EEH), and space motion sickness (SMS) is primarily a shift of the inner ear Ca++ homeostasis towards a higher concentration of free Ca++ in the fluid compartments and adjacent intracellular spaces. It is postulated that an increase of Ca++ in this system might affect the transduction process and other functions associated with Ca++, such as turnover of otoconia.

A new aspect in pathogenesis of experimental hydrops: role of calcium.

The pathological patterns of the sensory epithelium of the crista ampullaris of a guinea pig were studied after streptomycin and kanamycin administration. The silver reaction method and succinic dehydrogenase staining were applied for the entire surfaces of all specimens. Differences in sensitivity to antibiotics were confirmed in the sensory cells of the central and the peripheral regions of the crista (Lindeman, 1969 a).

A. Meyer zum Gottesberge

Papers

Physiology and Pathophysiology of Inner Ear Melanin

Changes in Ca++ activity and DC potential in experimentally induced endolymphatic hydrops.

Ca++ activity in the endolymphatic space

A new aspect in pathogenesis of experimental hydrops: role of calcium.

Toxic effects of streptomycin and kanamycin upon the sensory epithelium of the crista ampullaris.