Effects of noise on the nervous system.
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Animals↗
Biomedical subjects
A Flock
Publications and source records attributed to A Flock.
Mechanisms of movement in outer hair cells and a possible structural basis.
Isolated outer hair cells were found to slowly shorten when subjected to a solution that would induce contraction in a muscle fibre. Two possible mechanisms underlying this behaviour emerge from ultrastructural and immunocytochemical investigations. Antibody labelling at the electron microscopic level demonstrates that actin is present not only in the stereocilia and in the cuticular plate but also along the wall of outer hair cells, between the plasma membrane and the subsurface fenestrated cisternae. The latter are interconnected by regularly spaced pillars, resembling those seen between the T-tubules and sarcoplasmic reticulum in muscle fibres. Contraction also results from the application of positively charged macromolecules to the bathing solution. This implies sensitivity of the membrane-associated complex (the cortex system) to an electrical current. A second contractile system may reside in the cytoplasm, where calmodulin is present in contracted hair cells. This protein is a calcium-binding control protein for contraction-like events in smooth muscle and non-muscle cells. The unique presence of the cortex system in outer hair cells, and its absence in inner hair cells, indicates a functional significance that relates to a motor function of outer hair cells in hearing.
Actins↗
Changes in stereocilia micromechanics following overstimulation in metabolically blocked hair cells.
Previous studies have demonstrated that stereocilia micromechanics change during exposure to intense stimulation, and then recover after the stimulus has ended. These changes were associated with a loss of stiffness in the sensory hair bundle. The patterns of growth and recovery in these data suggest that active cellular processes control and limit these phenomena. The present investigation further supports this suggestion. The effects of intense stereocilia stimulation were examined before and after the hair cells were metabolically blocked by cooling or by poisoning with NaCN. In normal cells threshold shift increases with exposure duration, reaching a plateau within 5 to 6 min. Moreover, a post-exposure recovery of the threshold was also noted in the control cells within 15 min. In contrast threshold shift after the first minute in the metabolically blocked cells increased monotonically during the exposure without any indication of a plateau. Similarly, no post-exposure recovery of threshold shift was seen in the stereocilia bundles. These data support the hypothesis that metabolic processes in the region of the sensory hairs are important for limiting the loss of stiffness during exposure, as well as for restoring stiffness during recovery.
Animals↗
Recovery of threshold shift in hair-cell stereocilia following exposure to intense stimulation.
The isolated cochlear coil preparation was used to study changes in hair-cell stereocilia stiffness before and after overstimulation. Results were obtained from inner and outer hair cells in the apical and middle turns of the guinea pig cochlea. The stereocilia bundles were stimulated with an oscillating water jet and their movements were identified with stroboscopic illumination in a differential interference contrast microscope. The intensity of the water jet could be varied in decibel steps and the attenuation needed to achieve a 'visual detection level' threshold of movement was the criterion response throughout. Pre-exposure thresholds were sampled, the stereocilia bundle was overstimulated, and thresholds were measured during a recovery interval. Sensory hair bundles on all hair-cell rows showed a loss in stiffness following overstimulation which was proportional to the impedance of the stereocilia bundle. During recovery, stiffness increased and often showed a return to the pre-exposure threshold level. The results demonstrated that the loss of sensory hair stiffness following overstimulation recovered with the passage of time. The magnitude of the initial threshold shift, however, was related to the exposure conditions, cochlear location, and the impedance of the sensory hair bundle. The rate of recovery appeared to be independent of cochlear location, hair-cell row, or exposure conditions.
Acoustic Stimulation↗
Growth of threshold shift in hair-cell stereocilia following overstimulation.
Sensory hair bundle micromechanics were measured from all four hair-cell rows in the isolated guinea pig cochlea before and during overstimulation. The stereocilia bundle was stimulated by an oscillating water jet, and stroboscopic illumination slightly offset from the frequency of the stimulus revealed their motion. The intensity of the water jet could be varied in decibel steps and a 'visual detection level' threshold of stereocilia movement served as the criterion response. Pre-exposure thresholds provided a reference and were compared to thresholds sampled at 1-min intervals during a 10-min exposure period. The exposure stimulus consisted of the water jet adjusted to either 8, 13, or 18 dB above the visual detection level. Stereocilia on hair cells in each of the four rows showed a loss in stiffness which systematically increased during the first 5 to 6 min of exposure. Between 6 and 10 min of overstimulation the threshold shift exhibited a plateau whose magnitude was proportional to the exposure level. There were also differences in the magnitude of threshold shift between the hair-cell rows. The results clearly showed that overstimulation changed the micromechanical behavior of the stereocilia bundle, and that there was a complex interaction between exposure duration, level, and hair-cell row.
Acoustic Stimulation↗
Role of inner and outer hair cells in mechanical frequency selectivity of the cochlea.
Resonant frequencies of inner (IHC) and outer (OHC) hair cell systems in the guinea pig cochlea were computed using data on sensory-hair stiffness obtained from in vitro organ of Corti preparations (D. Strelioff and A. Flock (1984): Hearing Res. 15, 19-28). IHC stereocilia were modelled as stiff, free-standing, uniform cylinders which rotate about their elastic attachments to the apical surfaces of IHC. OHC, with the overlying tectorial membrane (TM), were modelled as a resonant mechanical system with the TM providing mass and the three rows of OHC sensory-hair bundles providing elasticity for linear, simple harmonic motion parallel to the reticular lamina. Since computed IHC resonant frequencies increase from 128 kHz at the apex to 300 kHz at the base, it is unlikely that they contribute to frequency selectivity. In contrast, computed frequencies of the OHC-TM system are within the audio range, increasing from 1.2 kHz at the apex to 22 kHz at the base. The results of these computations support the hypothesis that the OHC-TM system contributes to mechanical frequency selectivity of the cochlea whereas IHC are passive receptors which respond to mechanical movements of the cochlear partition.
Animals↗
Stiffness of sensory-cell hair bundles in the isolated guinea pig cochlea.
Stiffness of hair bundles on cochlear hair cells was measured in turns 2, 3 and 4 of isolated preparations of the guinea-pig organ of Corti maintained in tissue culture medium. Defined as the force required to produce a linear 1.0 micron deflection of the hair-bundle tip, stiffness is greater for deflection in the excitatory than in the inhibitory direction. The excitatory-to-inhibitory ratio for inner hair cells (IHC) is significantly lower than the ratio for outer hair cells (OHC). Hair-bundle stiffness decreases radially from the first to third rows of OHC. Over the measurement range of 9.0-18.0 mm from the stapes hair-bundle stiffness decreases much more for OHC (88-97%) than for IHC (50%). Although an increase in hair-bundle length with distance from the stapes accounts for some of the observed stiffness decrease, the major decrease is due to an increase in compliance of the sensory-hair attachment to the hair-cell surface.
Animals↗
Sensory hairs as mechanical filters in crista ampullaris: passive through structure and active through contraction.
The present text is a summary of original work describing individual variation in mechanical filter properties between different sensory hair bundles in the frog crista ampullaris. The difference relies on a variation of the degree of development of stereocilia within each bundle. Active control of mechanical properties is implied by the finding that media that would induce contraction in a muscle cell cause a restriction of motility of the sensory hairs.
Animals↗
Scanning electron microscope specimen preparation technique for dissociated strial marginal cells.
Single strial marginal cells from the cochleas of guinea pigs and chinchillas were successfully isolated in tissue culture medium using the enzyme dissociation technique. Such single cells were successfully preserved for scanning electron microscopic observation in special glass wells following the freeze drying technique. Judging by transmission electron microscopic examination of such cells, the ultrastructural preservation of the dissociated strial marginal cells was excellent.
Animals↗
Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.
After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylation↗
Micromechanical properties of sensory hairs on receptor cells of the inner ear.
The aim of the investigation was to obtain quantitative measures of mechanical filter properties of hair cell sensory hairs which were not restricted to move by auxiliary structures. The specimen used was the crista ampullaris of the frog, dissected free and positioned in a fluid-filled chamber where it could be viewed with differential interference contrast optics. The sensory hairs were displaced by a brief jet of frog Ringer's solution from a specially constructed microsyringe apparatus. The velocity of the jet could be stepwise controlled and was determined by measuring the speed of motion of 3 micron plastic beads propelled with the jet across the microscopic field. The stereocilia displacements were recorded on 16 min film, and both the angle of deflection and the time for the return to the resting position were measured on the film. It was found that after displacement the sensory hairs returned to the upright position by elastic properties in the hinge region at their insertion point in the cuticular plate. Sensory hairs differed in their speed of return so that some had fast time constants, others quite slow ones. This was correlated to a difference in structural development of the stereocilia, fast sensory hairs having thick and tall stereocilia, slow ones having thin and short stereocilia. The various bundle types were identified in the scanning electron microscope and their distribution on the crista was mapped. This was found to match the distribution of nerve fibres with different functional properties. It is concluded that sensory hair cells can differ in their mechanical filter properties as a result of the structural arrangement of their stereocilia and in accordance with functional demands.
Animals↗
Active control of sensory hair mechanics implied by susceptibility to media that induce contraction in muscle.
The motion of individual sensory hair bundles in the crista ampullaris was studied quantitatively by subjecting them to a brief jet of fluid in response to which they would swing away and then return by elasticity inherent at their insertion point. This motion was studied in media that would induce relaxation or contraction in a muscle system. The motion became severely restricted under conditions promoting contraction. Similar results were obtained by application to the organ of an ionophore that has the capacity to enter the cell membrane and allow influx of calcium ions. There was no effect of the ionophore in the absence of calcium ions. These results indicate that the sensory cells in the ear may possess a contractile machinery situated at the input end of the cell in the region of the sensory hairs and cuticular plate. The functional implication is that the mechanical input properties of the hair cells, and thus their excitability, can be under physiological control. It further implies that hair cells can produce a mechanical output in response to sensory or synaptic stimuli.
Actins↗
Ultrastructural studies of stereocilia in noise-exposed rabbits.
In rabbits with noise-induced, permanent hearing loss of more than 20 dB the stereocilia of the inner hair cells (IHCs) showed widespread signs of damage: fracturing, folding, fusion, and formation of giant hairs. Damage to the stereocilia on outer hair cells (OHCs) was much less pronounced in corresponding regions. On damaged OHCs the stereocilia were usually missing, except in the apical turn where fusion of stereocilia and formation of giant stereocilia occurred. On both IHCs and OHCs the 'neck' of the stereocilium appeared to be a site of fracture of the actin skeleton. On IHCs the actin cores of the former stereocilia were enclosed in a bulge of the apical cytoplasm to form a giant hair, with portions of the stereocilia projecting from the bulge. Inside the giant hairs profiles of the original stereocilia could be recognized, and these often retained their original circular form at least at the base of a giant hair. In the distal portion of the giant hair the actin filaments frequently formed a single thick bundle where the individual stereocilia could not be distinguished. Material had condensed between the surface membrane enclosing the former stereocilia and the actin cores. A thin kinocilium was often identified on IHCs. together with giant hairs possibly indicating a regenerative activation of the cell. It is suggested that fracture and fusion of stereocilia are due to different pathophysiological mechanisms, and that the actin of damaged cilia may undergo a slow reorganization and regeneration.
Actins↗
Intracellular recordings from cochlear outer hair cells.
Intracellular recordings were made from outer hair cells in the third turn of the guinea pig cochlea, and the electrical characteristics of the cells were compared to those of inner hair cells, supporting cells, and extracellular spaces from the same recording region. Outer hair cells have higher membrane potentials than do inner hair cells, but they produce smaller a-c receptor potentials. The frequency response characteristics of both types of hair cells are probably not significantly different. In the frequency region where tuning is optimal, both cell types produce depolarizing d-c receptor potentials, but outer hair cells also generate hyperpolarizing responses at low frequencies.
Action Potentials↗
Rods of actin filaments in type I hair cells of the Shaker-2 mouse.
The shaker-2 mouse with inherited inner ear disease suffers from deafness and a shaking-waltzing behavior. The hair cell type I in cristae ampullares and maculae utriculi show a specific pathology, featuring fusion of the stereocilia and presence of a rod-shaped inclusion body. The inclusion body is composed of filaments that could be identified as the protein actin by the method of decoration with subfragment S-1 of myosin. The functional polarity was determined, and S-1 fragments were found to point apically, that is, from the nucleus up toward the cuticular plate. These observations are identical to those earlier described in the waltzing guinea pig. It is concluded that the identical pathology at a cellular level in two different species may indicate a pathologic disorder in a process fundamental to the normal development of this type of hair cell.
Actins↗
Immunohistochemical localization of several cytoskeletal proteins in inner ear sensory and supporting cells.
Several structural and contractile proteins have been searched for with immunohistochemical methods using antibodies directed against these proteins. Three types of preparations from the guinea pig have been used: isolated stereocilia from the utricle, organ of Corti fragments obtained by cellular dissociation and 0.2-1 micrometer sections obtained by cryoultramicrotomy. The main finding is that different sets of proteins compose the cytoskeleton in supporting cells and the mechanoreceptor structures of the sensory cells. Thus, actin was found in association with fimbrin in the mechanoreceptive region of hair cells, whereas supporting cells, although rich in actin, did not reveal fimbrin. Instead tubulin was seen together with actin in supporting cells which also exhibited prekeratin. Fimbrin appears to function as a protein capable of making bundles and networks from actin filaments. Its exclusive presence in the mechanosensitive region of the sensory cells is possibly related to the function of these cells as mechanoreceptors.
Actins↗
Immunofluorescence localizations of proteins in semithin 0.2--1 micron frozen sections of the ear. A report of improved techniques including gelatin encapsulation and cryoultramicrotomy.
The present work describes a high resolution technique for locating proteins in frozen sections of the inner ear by immunofluorescence. Dissected organs are encapsulated in gelatin, and sections 0.1--1 micron thick are cut at --100 degrees C in a cryoultramicrotome. These are labelled with antibodies against two cytoskeletal proteins, actin and tubulin. Actin, which had previously only been described in the sensory cells, is found in the supporting cells as well. Tubulin is identified in the supporting cells and in outer spiral nerve fibres.
Actins↗
Three sets of actin filaments in sensory cells of the inner ear. Identification and functional orientation determined by gel electrophoresis, immunofluorescence and electron microscopy.
Receptor cells in the ear are mechanically excited through displacement of sensory hairs, stereocilia, in relation to a sub-surface platform, the cuticular plate, into which rootlets of the stereocilia insert. The presence of actin in inner ear sensory organs and receptor cells was established by gel electrophoresis, by labelling with antibodies against actin, and by electron microscopy after decoration with subfragment-1 of myosin. The latter method was used to determine the functional orientation of actin filaments found to be present in the mechanosensitive region of the receptor cells. Actin filaments were demonstrated in the stereocilia and their rootlets, in the cuticular plate and in relation to the zonula adherens surrounding the top of the cell. Filaments which run parallel to the cell surface were found in the cuticular plate and zonula adherens. Some filaments associated with the zonula adherens had a functional orientation opposite to that of more centrally located filaments in the cuticular plate. A structural complex consisting of a solid filament surrounded by actin filaments in hexagonal packing was found in the periphery of the cuticular plate. The possibility is suggested that the central filament is myosin.
Actins↗