Electrical filtering in gerbil isolated type I semicircular canal hair cells

1. Membrane potential responses of dissociated gerbil type I semicircular canal hair cells to current injections in whole cell current-clamp have been measured. The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25). Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current injections (from approximately -200 to 750 pA) produced only small-amplitude, pulse-like changes in membrane potential. 2. Injecting constant current to hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold increase in membrane resistance. Current pulses superimposed on this constant hyperpolarization produced larger and more complex membrane potential changes. Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A previously described K conductance, IKI, which is active at Vz, produces the low input resistance and frequency response. This was confirmed by pharmacologically blocking IKI. This conductance, present in type I cells but not type II hair cells, would appear to confer on type I cells a lower gain, but a much broader bandwidth at Vz, than seen in type II cells.     

Occlusion of the semicircular canal using argon laser

The effects of argon laser on the bony semicircular canals were studied in the guinea pig. After intraperitoneal administration of Nembutal, the bulla was opened in order to approach the lateral and posterior canals. The anterior canal was approached through the posterior fossa. The argon laser was applied through a probe which was connected to a device from HGM Medical Laser Systems. One of the three semicircular canals was irradiated one to several times by argon laser (1.0-1.5 W x 0.5 sec). Histopathologic examination of the temporal bones revealed that the semicircular duct shrank immediately after irradiation. The laser produced a charred area in the bony canal wall. The semicircular canals gradually became fibrotic and ossified and completely occluded within several weeks. Heat produced in the bony canal may be responsible for the morphologic changes. On delayed observation, the cochlea of the canal-irradiated animals showed no morphologic changes. Auditory brain stem responses were normal. Caloric stimulation using 5 ml/5 sec of ice water revealed no response in the lateral canal-irradiated animals.     

Benign postural vertigo and nystagmus of the horizontal semicircular canal

Benign paroxysmal vertigo and nystagmus are induced not only by the posterior but also by the horizontal semicircular canal. Benign positional nystagmus of the horizontal canal is more often observed than was previously thought. In 10 patients we analyzed the characteristics and the variability of nystagmus which accompanies positional vertigo of the horizontal canal. There are two forms of nystagmus: primary-geotropic, most often paroxysmal nystagmus (7 patients), and primary-apogeotropic, non-paroxysmal nystagmus (3 patients). Interestingly, in 2 patients with the primary-apogeotropic form the nystagmus converted during the examination into the primary-geotropic form. The reverse was not observed. We discuss the possible pathophysiological mechanisms which could be relevant for provoking manoeuvres.     

Unilateral peripheral semicircular canal lesion and off-vertical axis rotation

Aqueous extracts of Goniopora tenuidens inhibited larval metamorphosis and post-metamorphic growth of the hard coral Pocillopora damicornis. The extracts killed swimming larvae of four scleractinian corals and modified the behaviour of larvae of P. damicornis at concentrations as low as 3.9 micrograms ml-1. This toxicity may indicate the presence of allelochemicals that limit the settlement of potential competitors.     

Arrangement of vestibular nerve fibers in the semicircular canal crista of the chinchilla

The topographic arrangement of vestibular nerve fibers innervating semicircular canal cristae of the chinchilla was studied using computer-aided video-microscopy and three-dimensional reconstruction. At the level 20 microns proximal to the base of the crista, bundles consisting of 30-50 nerve fibers each were identified. Nerve fibers in bundles were classified into seven categories depending on the diameter. We confirmed that large nerve fibers were more frequently found in the central bundles and small nerve fibers were more frequently found in the peripheral bundles. The central bundle might function as a physiological unit coding various types of head movements, whereas the peripheral bundle might contribute more to the detection of slow and long-lasting movements giving rise to tonus and posture changes. The canalicular nerve may code rotational acceleration of the head via function- and locus-specific nerve fiber bundles.     

Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity

Recovery of semicircular canal primary afferent activity in the pigeon after streptomycin ototoxicity. J. Neurophysiol. 80: 3297-3311, 1998. The electrophysiological activity of horizontal semicircular canal primary afferents (HSCPA) was investigated in vivo in the barbiturate-anesthetized pigeon by means of extracellular single-fiber vestibular nerve action potential recordings. The spontaneous and driven discharges to pulse (step/trapezoid waveform, peak velocity = 120 degrees/s) and sum-of-sines (0.03, 0.09, 0.21, 0.39, 0.93, 1.83 Hz, peak velocity = 30 degrees/s for each frequency) rotations were measured both in normal control animals and a group of animals at 30, 40, 50, 60, 71, and 150 days postinjection sequence (PIS) of streptomycin sulfate. Prior to 30 days PIS, the activity in the nerve was not appropriately modulated during and after rotation. At 30 days PIS and thereafter, the responses resembled those observed in control animals but with systematic changes in parameters of fitted pulse responses and fitted Bode plots as days PIS increased. The return of parameters characterizing the neural dynamics of the semicircular canals were monotonic and could be best described by either linear or exponential functions. After 30 days PIS, the mechanical cupula-endolymph system, the function of which can be inferred from the cupula long time constant (tauL) following step velocity, did not change systematically (tauL = 6.92 +/- 3.96, 8.64 +/- 5.52, 8.35 +/- 4.21, 10.00 +/- 2.79, 9.05 +/- 3.67, 7.05 +/- 2.72; means +/- SD). However, the mean gain (G) of the HSCPA response to pulse rotation nearly doubled between 30 and 150 days PIS (from 1.31 +/- 0. 39 to 2.40 +/- 1.04) and returned linearly to control values (G = 2. 39 +/- 0.77) over this time period [G = 1.33 + 0.009(PIS-30), R2 = 0. 92, P < 0.05]. Meanwhile, neural adaptation as quantitated using a fractional operator, k, decayed exponentially (single exponential) to an asymptote. The time constant of this exponential was approximately 55 days [k = 0.034 + 0.33e-(PIS-30)/55.4, R2 = 0.99, P < 0.01]. Features of the spontaneous discharge previously shown to be correlated with k changed appropriately. That is, the coefficient of variation (CV) and frequency of firing (FF) decayed and grew asymptotically, respectively. These parameters also exhibited an exponential time course of return to control values from 30 to 150 days PIS [CV = 0.44 + 0.65e-(PIS-30)/21.5, R2 = 0.96, P < 0.01, and FF = 39.97 + 101.42(1 - e-(PIS-30)/32.6), R2 = 0.97, P < 0.01]. The trends of recovery for G, k, and tauL derived from analysis of the pulse response were confirmed by strong positive correlations with best fitted parameters obtained from analysis of the sum-of-sines frequency domain response of HSCPAs. There were statistically significant correlations (r = 0.90, P < 0.05 and r = 0.93, P < 0.05) between parameters (G, k) derived from pulse responses and those (G', k') from sum-of-sines responses, respectively. The cupula time constant based on sum-of-sines' data (tau'L) showed no statistically significant change between 30 and 150 days PIS (P > 0.05, analysis of variance). Thus the results in present study indicate that both the spontaneous discharge and the driven response to rotation of pigeon HSCPAs recovered their normal physiological status between 30 and 150 days PIS after hair cell death due to aminoglycoside ototoxicity. The recovery was systematic for the parameters chosen to be tested with the exception of the cupula long time constant, tauL. The mechanisms (changes in ciliary dynamics, changes in hair cell ionic currents, changes in bouton terminals, etc.) underlying these changes await further morphophysiological studies.     

Otolith and semicircular canal contributions to the human binocular response to roll oscillation

Transferrin (Tf) is required for proliferation of most cells, because cellular iron uptake is mainly mediated by binding of Tf to its specific cell surface receptors (TfR). The acute-phase protein alpha 1-antitrypsin (alpha 1-AT) completely inhibits binding of diferric Tf to TfRs on human skin fibroblasts in a dose-dependent fashion. The inhibition is competitive as proved in equilibrium saturation binding and kinetic studies. In saturation binding experiments alpha 1-AT apparently increased the dissociation constant (KD), but did not change the maximal density of binding sites (Bmax). As shown in kinetic studies, this reduction of the affinity of Tf to its receptor caused by alpha 1-AT was due to a decrease of the association rate constant (k + 1), whereas the dissociation rate constant (k - 1) remained unchanged. Furthermore, alpha 1-AT almost completely prevented internalization of the Tf-TfR complex. These interactions demonstrated biological implication, as alpha 1-AT reduced the proliferation of human fibroblasts up to maximal 30% of control. The inhibitory potency of alpha 1-AT was already seen in physiologic concentrations; the maximal effect, however, was achieved at concentrations above the normal range, which are attained in the course of inflammation and infection. Therefore, we suppose that alpha 1-AT as an endogenous factor modulates the complex mechanism of fibrogenesis not only by its known antiproteolytic function but also by inhibiting the proliferation of fibroblasts.     

Mechanics of caloric stimulation in a case with a plug in the horizontal semicircular canal

Cytochrome P-450cam hydroxylates d-camphor, using molecular oxygen and reducing equivalents transferred via putidaredoxin. We constructed mutant genes in which Phe-350 of P-450cam was replaced by Leu, Tyr, or His by site-directed mutagenesis, expressed them in Escherichia coli, purified the mutant proteins, and compared their enzymic properties with those of the wild type P-450cam. NADH oxidation rate of the Tyr mutant in the reconstituted system with putidaredoxin and putidaredoxin reductase was similar to that of the wild type enzyme, while the Leu mutant and the His mutant showed 67% and 17% activity of that of the wild type, respectively. The affinities of these mutant proteins for camphor and the oxidized form of putidaredoxin were much the same as those of the wild type protein. Rate constants for the reduction reaction of P-450cam by reduced putidaredoxin, a physiological electron donor for P-450cam, of Tyr and His mutants were much the same as that of the wild type enzyme, whereas the Leu mutant showed approx. half that of the wild type. Thus, the aromatic ring of Phe-350 of P-450cam probably contributes to enhancing efficiency of the electron transfer yet does not seem to be essential for the reaction.     

Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal

From 1965 to 1990, the prevalence of cigarette smoking among US adults (aged > or = 18 years) fell steadily and substantially. Data for the 1990s suggest that the smoking initiation rate is increasing and that the decline in the prevalence of smoking may have stalled, raising the fear that the historical 25-year decline will not continue. The authors used a new dynamic forecasting model to show that although the decline may slow down, the demographics of smoking imply that prevalence will inexorably continue to decline over the next several decades, even without any intensified efforts aimed at tobacco control. The authors estimated and validated the model using historical (1965-1993) data collected by the National Health Interview Surveys on the prevalence of smoking among adults. Their results indicate that the current increase in the smoking initiation rate partially explains the fact that the prevalence of smoking has apparently leveled off, but even if the most grim assumptions about future initiation rates are used, the prevalence of smoking among adults will continue to decline for several more decades. The authors predict that if current initiation and cessation behaviors persist, the prevalence of smoking among adults will automatically decline from its current level of 25% to 15-16% by the second quarter of the next century. Even so, smoking will remain the nation's leading cause of premature death.     

The response of primary horizontal semicircular canal neurons in the rat and guinea pig to angular acceleration

In rats and guinea pigs, primary afferent neurons from the horizontal semicircular canal were divided into two categories, regular and irregular, on the basis of the regularity of their resting activity. Regular neurons tend to have higher average resting rates than irregular neurons and in response to a constant angular acceleration stimulus of 16.7 deg/s2 regular neurons tended to have lower sensitivity and longer time constants than irregular cells. Some irregular neurons are more sensitive to incremental accelerations than to decremental accelerations of the same magnitude, whereas regular neurons tend to show symmetrical sensitivity. In response to sinusoidal angular acceleration stimuli (fixed frequencies) in the range 0.01-1.5 Hz, cells which fired regularly at rest tended to have smaller gain and longer phase lag re acceleration at most frequencies than irregular cells. Transfer functions were obtained for averaged data for regular and irregular neurons separately in both species. In both species there is evidence of systematic variation between neurons within each category, and this systematic variation is obscured by averaging across neurons.     

Ambroxol effect on transepithelial electrical potential difference of isolated tracheal wall

We report a laser microprobe mass analysis of aluminum and iron content in the hippocampus and in the inferior temporal cortex in 2 cases of dementia pugilistica (DP), 4 cases of Alzheimer's disease (AD), and 3 controls. There was a predominant accumulation of Al and Fe within neurofibrillary tangles (NFT) in both DP and AD cases. High levels of Al and Fe were also detected in the nuclei of NFT-free and NFT-containing neurons, as well as in neuropil probe sites in these cases. In both regions, NFT contained substantially higher levels of Al and Fe in DP compared to AD cases. These findings suggest the existence of an association between the deposition of Al and Fe and NFT formation, and support the possibility of a global dysregulation of Al and Fe transport in DP and AD.     

Compensation of the human vertical vestibulo-ocular reflex following occlusion of one vertical semicircular canal is incomplete

The vestibulo-ocular reflex (VOR) was studied in nine human subjects 2-15 months after permanent surgical occlusion of one posterior semicircular canal. The stimuli used were rapid, passive, unpredictable, low-amplitude (10-20 degrees), high-acceleration (3000-4000 degrees/s2) head rotations in pitch and yaw planes. The responses measured were vertical and horizontal eye rotations, and the results were compared with those from 19 normal subjects. After unilateral occlusion of the posterior semicircular canal, the gain of the head-up pitch vertical VOR--the vertical VOR generated by excitation from only one and disfacilitation from two vertical semicircular canals--was reduced to 0.61 +/- 0.06 (normal 0.92 +/- 0.06) at a head velocity of 200 degrees/s. In contrast the gain of the head-down pitch vertical VOR--the VOR still generated by excitation from two, but disfacilitation from only one vertical semicircular canal--was within normal limits: 0.86 +/- 0.11 (normal 0.96 +/- 0.04). The gain of the horizontal VOR in response to yaw head rotations--ipsilesion 0.81 +/- 0.06 (normal 0.88 +/- 0.05) and contralesion 0.80 +/- 0.11 (normal 0.92 +/- 0.11)--was within normal limits in both directions (group means +/- two-tailed 95% confidence intervals given in each case). These results show that occlusion of just one vertical semicircular canal produces a permanent deficit of about 30% in the vertical VOR gain in response to rapid pitch head rotations in the excitatory direction of the occluded canal. This observation indicates that, in response to a stimulus in the higher dynamic range, compensation of the human VOR for the loss of excitatory input from even one vertical semicircular canal is incomplete.     

Effects of extracellular ATP on hair cells isolated from the guinea-pig semicircular canals

Using stereological methods, two cerebral cortical areas from AIDS brains were investigated. Neuronal density, profile area of neurons, and perikaryon volume fraction were measured and compared to age-matched control brains. In the fronto-orbital cortex (area 11) of AIDS brains, a significant loss of neurons was seen. The perikaryon volume fraction was likewise decreased. The size of neurons did not differ between control and AIDS brains. In patients with clinical signs of progressive dementia and in brains with human immunodeficiency virus (HIV)-specific neuropathology (HIV-leukoencephalopathy and/or HIV-encephalitis) as compared to patients lacking these features, a small decrease in neuronal density was noted but this difference did not reach the level of statistical significance (P = 0.16). In the superior parietal lobule (area 7) of AIDS brains, no loss of nerve cells was noted. AIDS patients with progressive dementia and brains with HIV-specific neuropathology showed no difference in neuronal densities as compared to those without such features. We conclude that the fronto-orbital cortex, in contrast to the parietal cortex, is mainly damaged in AIDS brains. Neuronal loss was not significantly correlated with development of dementing symptoms and of HIV-specific neuropathology.     

Spatial transformation of semicircular canal signals into abducens motor signals. A comparison between grass frogs and water frogs

The spatial transformation of semicircular canal signals to extraocular motor signals was studied by recording abducens nerve responses in grass and water frogs. Both species have similar vestibular canal coordinates but dissimilar orientations of their optic axes. Before sinusoidal oscillation in darkness the static head position was systematically altered to determine the planes of head oscillation in pitch and roll associated with minimal abducens nerve responses. Measured data and known canal plane vectors were used to calculate the abducens response vector in canal coordinates. The abducens vector deviated from the horizontal canal plane vector in grass frogs by 15 degrees and in water frogs by 34 degrees but was aligned with the pulling direction of the lateral rectus muscle in each of the two species. Lesion experiments demonstrated the importance of convergent inputs from the contralateral horizontal and anterior semicircular canals for the orientation of the abducens response vector. Thus, the orientation of the optic axis and the pulling directions of extraocular muscles are taken into account by the central organization of vestibulo-ocular reflexes. Horizontal and vertical canal signals are combined species-specifically to transform the spatial coordinates of sensory signals into appropriate extraocular motor signals.     

Social identification effects in group polarization.

Tested a model of group polarization derived from social identity theory, proposing that if group members conform to group norms, attitude polarization could occur only if group members perceive those norms as more extreme than they "objectively" are. In Exp I, 60 undergraduates perceived attitude-relevant information attributed to speakers who were categorized as a group as representing a more extreme position of the issue than when the same information was attributed to noncategorized individuals. Attitude polarization occurred when Ss believed the information came from their in-group. As predicted, this polarization resulted from Ss' adoption of the "extremitized" in-group norm. In Exp II, categorization was manipulated by focusing 42 Ss on their group performance or on their individual performance. When Ss were focused on their group membership, group norms were perceived as more extreme, and attitude polarization due to conformity to these extremitized norms occurred. When Ss were focused on their individual performance, no extremitization occurred, and attitudes shifted to a more neutral position on the issue. (34 ref) (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Mechanisms of the glycaemic effects of sulfonylureas

Sulfonylureas are widely used to treat non-insulin dependent diabetes mellitus. These drugs exert their hypoglycaemic effects by stimulating insulin secretion from the pancreatic beta-cell. Their primary mechanism of action is to close ATP-sensitive K-channels in the beta-cell plasma membrane, and so initiate a chain of events which results in insulin release. Recent studies have shown that the beta-cell ATP-sensitive K-channel is a complex of two proteins: a pore-forming subunit (Kir6.2) and a drug-binding subunit (SUR1) which functions as the receptor for sulfonylureas. This review summarizes recent advances in our understanding of the molecular mechanism of sulfonylurea action, focusing on the relationship between the sulfonylurea receptor and the K-ATP channel. Earlier studies are also re-examined in the light of new findings.