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PubMed1985

The effect of loop diuretics upon summating potentials in the guinea pig.

Ototoxic diuretics, ethacrynic acid (50 mg/kg) and furosemide (80 mg/kg) were injected intravenously in guinea pigs. Cochlear microphonics (CM), summating potentials (SPs) and endocochlear potential (EP) were recorded with a microelectrode in scala media of the second turn. CM changes after the injection were comparable with changes in the EP: an initial decrease was followed by an increase which was significantly slower in the case of the ethacrynic acid. SP changes following either diuretic were different from the CM and EP changes. In the first phase, roughly corresponding with the EP decrease to negative values, all SPs irrespective of the original polarity, attained high positive values. The high positive SPs then decreased and 12-18 min after injection reversed polarity. In the late phase all sounds evoked high negative SPs. Approximately 90 min after injection of furosemide normal SPs were again recorded. The return of SPs to control values was very slow after ethacrynic acid; even 140 min after injection the SPs were abnormal. The observed changes in the SPs were compared with those found during asphyxia and anoxia and are considered to result from diuretic effects on the inner and outer hair cells.

Animals↗
PubMed1981

Development of cochlear potentials in rats.

The development of cochlear function was studied in 81 rat pups by recording the cochlear microphonic (CM) and the compound action potential (AP) from the round window in response to tone bursts and filtered clicks of various frequencies. The first electrophysiological response was the CM which could be obtained from 8- to 9-day-old animals. The AP first appeared at 11-12 days. As development progressed, cochlear potentials showed systematic changes in response parameters: the amplitude and threshold sensitivity of both CM and AP increased progressively with age as N1 latency decreased. All the parameters were within the adult range by the 15th day for the CM and by the 4th week for the AP. The results are discussed in relation to the developmental changes in the middle ear and to the morphological maturation of the organ of Corti.

Animals↗
PubMedDate not supplied

The effect of injection of high K+ solution into scala media.

Thirty guinea pig ears were studied to investigate the effect of endolymphatic hydrops on the cochlea. High K+ solution was injected into the scala media, and cochlear microphonics (CM) and endocochlear potential (EP) were observed before, during and after the injection. The CM amplitude decreased rapidly after injection, ending in a depressed plateau value. By contrast, EP remained almost unchanged. By changing the composition of the solution it was suggested that the effect of the injection was mechanical one, rather than biochemical. In three ears, spontaneous recovery of CM was observed during a relatively long interval after the injection. The meaning of these findings for the hearing loss in Meniere's disease is discussed.

Animals↗
PubMed2002

Auditory temporal resolution in birds: discrimination of harmonic complexes.

The ability of three species of birds to discriminate among selected harmonic complexes with fundamental frequencies varying from 50 to 1000 Hz was examined in behavioral experiments. The stimuli were synthetic harmonic complexes with waveform shapes altered by component phase selection, holding spectral and intensive information constant. Birds were able to discriminate between waveforms with randomly selected component phases and those with all components in cosine phase, as well as between positive and negative Schroeder-phase waveforms with harmonic periods as short as 1-2 ms. By contrast, human listeners are unable to make these discriminations at periods less than about 3-4 ms. Electrophysiological measures, including cochlear microphonic and compound action potential measurements to the same stimuli used in behavioral tests, showed differences between birds and gerbils paralleling, but not completely accounting for, the psychophysical differences observed between birds and humans. It appears from these data that birds can hear the fine temporal structure in complex waveforms over very short periods. These data show birds are capable of more precise temporal resolution for complex sounds than is observed in humans and perhaps other mammals. Physiological data further show that at least part of the mechanisms underlying this high temporal resolving power resides at the peripheral level of the avian auditory system.

Animals↗
PubMed1982

Minimal concentrations of metabolic substrates capable of supporting cochlear potentials.

The objective of this study was to determine the capability of glucose analogues, as well as lactate and pyruvate, to maintain the endolymphatic potential and the cochlear microphonics. In addition, the minimum concentration at which different substrates (including D-glucose) were able to sustain the potentials ("critical' concentration) was determined. Synthetic blood containing various substrates at different concentrations was perfused via the anterior inferior cerebellar artery. The critical concentration for D-glucose was found to be 15 mg% (0.83 mM). L-Glucose, galactose and fructose were not able to support the potentials at concentrations as high as 200 mg%. On the other hand, mannose was capable of supporting the potentials; however, the critical concentration (50 mg% or 2.8 mM) was substantially higher than that of D-glucose. Both lactate and pyruvate could support the potentials, but the critical concentrations (8.5 mM and 6.5 mM, respectively) were markedly higher than in the case of glucose, even when the difference of carbon equivalents was taken into consideration. The data are discussed in the context of the intermediary metabolism and possible carrier systems of the stria vascularis.

Action Potentials↗
PubMed1997

Methods for integrating fluorimetry in the study of hearing organ structure and function.

The measurement of function in the intact organ of Corti has up to now been achieved by three methods: electrophysiology, mechanical measurement and biochemical analysis. The two former methods have supplied information at the level of single identified cells. We have used a fourth method, optical fluorimetry, to measure hair cell function at the cellular level in the intact organ of Corti. Here we describe the methods involved in fluorescence labelling and video-enhanced microscopy in combination with electrophysiological recording of cochlear microphonic (CM) and summating potentials (SP). The guinea pig temporal bone containing an intact ear drum, ossicular chain and cochlea can be maintained in the isolated state by perfusion of the scala tympani with oxygenated tissue culture medium. Substances added to the perfusate readily diffuse through the basilar membrane into the organ of Corti. In this way cells in the organ can be stained by a number of fluorescent probes which label different structures and functions. Here we have used two dyes which label mitochondria and fluoresce with an intensity proportional to metabolic activity. By simultaneous measurement of CM and SP the functional state of the organ can be monitored.

Acoustic Stimulation↗
PubMed1995

Extracellular adenosine 5'-triphosphate (ATP) in the endolymphatic compartment influences cochlear function.

There is strong evidence for the presence of P2 purinoceptors on cochlear tissues, but the role of extracellular ATP in cochlear function is still unclear. Our previous studies have determined the presence of ATP in the cochlear fluids and indicated that the purinoceptors are substantially localized to the tissues lining the endolymphatic compartment. This implies that extracellular ATP may have an humoral role confined to the endolymphatic space. In order to study the influence of extracellular ATP in the endolymphatic space, a series of studies were undertaken in which ATP (10 microM to 10 mM) in artificial endolymph (EL) (test solution: 2-12.5 nl) was injected into the scala media and the effect on the cochlear microphonic (CM) and endocochlear potential (EP) evaluated. A double-barrelled pipette, with one barrel containing the test solution and the other artificial EL (control solution) was inserted into scala media of the third turn of the guinea-pig cochlea. A known volume (2-12.5 nl) of test or control solution was then pressure-injected into the space. ATP had a significant dose-dependent suppressive effect on both EP and CM with a threshold of approximately 2 x 10(-14) mol; the response was readily reversible, also in a dose-dependent fashion. Artificial EL of the same volume had no effect on EP and CM. The ATP effect on EP was blocked by the P2 purinoceptor antagonists suramin and reactive blue 2 (RB2). Neither adenosine (2 x 10(-13) to 2 x 10(-11) mol) nor suramin or RB2 on their own had any effect on EP and CM. This study provides the first evidence for an effect of extracellular ATP in the endolymphatic compartment on cochlear function which is mediated via P2 purinoceptors. This provides supporting evidence for an humoral role for extracellular ATP in the modulation of cochlear function.

Adenosine↗
PubMed1998

The effect of forskolin on the sound-evoked potentials in the guinea pig cochlea.

The effect of forskolin (FSK) on cochlear sound-evoked potentials was examined in the guinea pig. The perfusion of the scala vestibuli (SV) with FSK (2 x 10(-4) M) produced a significant increase in the amplitude of negative summating potential (- SP) with no change in cochlear microphonics (CM) amplitude, and a significant decrease in the amplitude of compound action potential (CAP) with a significant prolongation of N1 latency and a 20 dB CAP threshold elevation. The results lead us to speculate that FSK-induced changes may be involved in the transient formation of endolymphatic hydrops.

Animals↗
PubMed2003

Thapsigargin suppresses cochlear potentials and DPOAEs and is toxic to hair cells.

Thapsigargin, a drug that inhibits sarco-endoplasmic reticulum Ca(2+) ATPases (SERCAs), was infused into the perilymph compartment of the guinea pig cochlea in increasing concentrations (0.1-10 microM) while sound evoked cochlear potentials were monitored. Thapsigargin significantly suppressed the compound action potential of the auditory nerve, cochlear microphonics, and increased N(1) latency at low (56 dB SPL) and high intensity (92 dB SPL) levels of sound, suppressed low intensity sound evoked summating potential (SP) and greatly increased the magnitude of the high intensity sound evoked SP. At 10 microM, the drug suppressed the cubic distortion product otoacoustic emissions (2f(1)-f(2)=8 kHz, f(2)=12 kHz) evoked by both high and low intensity primaries (45, 60, 70 dB SPL). Thapsigargin (10 microM; 30 min) increased the endocochlear potential slightly (5 mV). In chronic animals, thapsigargin (10 microM; 60 min) destroyed many outer hair cells and some inner hair cells, especially in the basal turns. These effects are consistent with the hypothesis that the inhibition of the SERCAs affects the function of the cochlear amplifier and outer hair cells to a greater degree than it affects other functions of the cochlea.

Acoustic Stimulation↗
PubMed2001

Effect of inner and outer hair cell lesions on electrically evoked otoacoustic emissions.

When the cochlea is stimulated by a sinusoidal current, the inner ear emits an acoustic signal at the stimulus frequency, termed the electrically evoked otoacoustic emission (EEOAE). Recent studies have found EEOAEs in birds lacking outer hair cells (OHCs), raising the possibility that other types of hair cells, including inner hair cells (IHCs), may generate EEOAEs. To determine the relative contribution of IHCs and OHCs to the generation of the EEOAE, we measured the amplitude of EEOAEs, distortion product otoacoustic emissions (DPOAEs), the cochlear microphonic (CM) and the compound action potential (CAP) in normal chinchillas and chinchillas with IHC lesions or IHC plus OHC lesions induced by carboplatin. Selective IHC loss had little or no effect on CM amplitude and caused a slight reduction in mean DPOAE amplitude. However, IHC loss resulted in a massive reduction in CAP amplitude. Importantly, selective IHC lesions did not reduce EEOAE amplitude, but instead, EEOAE amplitude increased at high frequencies. When both IHCs and OHCs were destroyed, the amplitude of the CM, DPOAE and EEOAE all decreased. The increase in EEOAE amplitude seen with IHC loss may be due to (1) loss of tonic efferent activity to the OHCs, (2) change in the mechanical properties of the cochlea or (3) elimination of EEOAEs produced by IHCs in phase opposition to those from OHCs.

Action Potentials↗
PubMed2005

[Effect of glutamate on distortion product otoacoustic emission and auditory brainstem response in guinea pigs].

OBJECTIVE: To investigate the changes of the potentials and structure of the guinea pig cochlear during whole cochlear perfusion with glutamate. METHODS: Cochlear microphonics (CM), compound action potential (CAP), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) were measured to indicate the cochlear functional properties during whole cochlear perfusion. The morphology of the cochlear was monitored by transmission electron microscopy. RESULTS: There were no significant DPOAE changes before and after glutamate perfusion. CM I/O function maintained a nonlinear characteristic during infusion. After glutamate perfusion, ABR latencies were delayed. There was significant difference in CAP threshold before and after glutamate perfusion. The average CAP threshold was elevated 35 dB. The OHCs appeared normal, but IHCs and afferent dendrites showed cytoplasmic blebs after glutamate infusion. CONCLUSIONS: Glutamate is thought to be a primary amino acid neurotransmitter at the synapses formed by cochlear hair cells and spiral ganglion neurons. However, the excessive glutamate is neurotoxic for cells, and it can destroy the IHCs and spiral ganglion neurons. The present method can also be built up as an animal model of auditory neuropathy.

Animals↗
PubMed1994

Lipid peroxidation inhibitor attenuates noise-induced temporary threshold shifts.

The purpose of this study was to investigate the protective effects of U74389F (Upjohn Co. Kalamazoo, MI), a 21-aminosteroid/lipid peroxidation inhibitor, and a member of the lazaroid drug class, on temporary threshold shifts in animals exposed to prolonged noise stimulation. Animals treated with U74389F and exposed to noise showed attenuated cochlear action potential threshold (CAP) shifts and cochlear microphonic (CM) when compared to non-drug treated noise-exposed subjects. These data suggest that inhibition of FOR induced lipid peroxidation is an important mechanism in noise-induced asymptotic temporary threshold shifts.

Acoustic Stimulation↗
PubMed1986

Analysis of cochlear mechanics.

A large number of experimental results on basilar-membrane vibration, cochlear microphonics, hair-cell receptor potentials, and spike rates in auditory nerve afferents are brought together to arrive at a comprehensive concept of cochlear mechanics, including hair-cell stimulation. Beginning with basilar-membrane tuning curves, we note that some of their most detailed determinations reveal a small notch and a secondary maximum above the best frequency in addition to sharp tuning. These features tend to become more prominent as the sharpness of tuning decreases. They cannot be accounted for on the assumption that the cochlear partition represents a simple second-order system consisting of distributed, elastically suspended mass. A higher order system is required. The cross-sectional structure of the partition suggests a fifth-order system made up of two sets of distributed resonators, one consisting essentially of the distributed mass of the organ of Corti supported by the stiffness of the basilar membrane, the other of the tectorial-membrane mass and its elastic attachment to the spiral limbus. The stiff stereocilia of the outer hair cells appear to serve as the main elastic coupling between the two resonator sets. Interaction of the two resonator sets is brought into evidence particularly clearly by weakening the coupling between the tectorial membrane and the organ of Corti. This can be achieved by manipulating the tectorial membrane with a microelectrode without affecting the endolymphatic potential. The partial decoupling leads to a transformation of a unimodal CM transfer function into a bimodal one. Except for the stiffness of the tectorial-membrane attachment to the limbus, the masses and stiffnesses involved in the two coupled resonator systems can be estimated independently on the basis of available measurements. Their application to an approximate computer model of the cochlea produced a cochlear frequency map consistent with experimental findings. The computer model, whose elements are in one-to-one correspondence with the gross elements of the cochlear partition, reproduces approximately the fundamental amplitude and phase characteristics of the measured basilar-membrane vibration. In particular, it reproduces the notch and the secondary maximum located above the best frequency. Our current computer model is linear and does not reproduce the known cochlear distortion products. Nevertheless, variation of those of its stiffness and resistance elements that correspond to the hair-cell stereocilia has allowed us to reproduce typical changes in basilar-membrane vibration, which accompany changes in sound intensity or cochlear deterioration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

ATP antagonists cibacron blue, basilen blue and suramin alter sound-evoked responses of the cochlea and auditory nerve.

The P2-purinergic receptor antagonists suramin, cibacron blue and basilen blue, the latter two being isomers of reactive blue 2, were studied for their effects on sound-evoked responses from the cochlea (cochlear microphonic, CM; summating potential, SP; distortion product otoacoustic emissions, DPOAE) and auditory nerve (compound action potential, CAP). Local application of these compounds (10-1000 microM) into the cochlear perilymph was associated with concentration-dependent response alterations. Effects of suramin on cochlear responses were minimal: High-intensity SP was reduced slightly at concentrations > or = 330 microM without significant alterations in CM or DPOAEs. The amplitude of the auditory nerve CAP was suppressed and its latency increased at drug concentrations > or = 100 microM. Cibacron blue and basilen blue were of greater potency in their effects on cochlear and auditory nerve responses. DPOAEs were generally reduced, low-intensity SP was reduced and high-intensity SP was increased and CM was little affected at drug concentrations 100-1000 microM. The CAP was suppressed and its latency increased at concentrations > or = 33 microM. Effects of suramin were largely reversible; those associated with cibacron blue and basilen blue generally were not. To the extent that these drugs acted selectively as antagonists of ATP receptor-mediated activity, results support the hypothesis that endogenous ATP exerts profound actions at the level of the cochlea and the auditory nerve.

Action Potentials↗
PubMed1996

[Effects of thapsigargin and ryanodine on cochlear electrical potentials in guinea pigs examined by the perilymphatic perfusion method].

The effect of thapsigargin and ryanodine on cochlear microphonics (CM) and the endocochlear DC potential (EP) in the guinea pig was investigated by the perilymphatic perfusion method. These chemicals were considered to be pharmacological tools to reduce the amount of Ca2+ stored within the endoplasmic reticulum (ER), although the sites of their action were different; thapsigargin inhibits Ca2+ uptake of the ER, while ryanodine locks Ca2+ channels of the ER in an open state. Both CM and EP were measured with a glass microelectrode inserted into scala media. The amplitude of CM started to decrease soon after the beginning of thapsigargin perfusion and fell to 35% of the initial value in 30 minutes. Ryanodine, like thapsigargin, reduced the CM amplitude depending on the concentration between 1 x 10(-6) approximately 3 x 10(-5)M. These results suggest that Ca2+ ions which regulate the ciliar movements of outer hair cells are due not only to entry from extracellular fluid but to their release from the intracellular storage sites, probably through the mechanisms of Ca(2+)-induced Ca2+ release.

Animals↗
PubMedDate not supplied

Effect of perilymphatic air perfusion on cochlear potentials.

Perilymphatic fistula is now widely recognized to cause acute profound hearing loss. It is still controversial, however, which mechanism it is that causes the reversible hearing loss. Recently, it has been suggested by two groups of researchers that the intrusion of air bubbles into the perilymphatic space (a condition called pneumolabyrinth or aerolabyrinth) through the ruptured labyrinthine window(s) may be one of the causes. In order to examine the mechanism underlying the hearing loss associated with pneumolabyrinth, the perilymphatic space of the guinea pig cochlea was perfused with air and cochlear potentials were recorded. Although perfusion of the scala tympani with air at a rate as high as 200 microliter/min caused an immediate and drastic decrease of the cochlear microphonics (CM) and the compound action potential (AP), it had little effect on the endocochlear dc potential (EP) during perfusion for 20 min. A decline in EP was seen in half the ears, but only when the duration of perfusion exceeded 30 min. These results show that the EP has an amazing resistance to air trapped in the scala tympani of the cochlea and that the initial decrease of hearing acuity after the elimination of perilymph from the scala tympani (or introduction of air into the scala tympani) is probably due to interference in CM and AP generation mechanisms rather than to strial dysfunction.

Action Potentials↗
PubMed1982

Ultrastructural and electrophysiological studies of acute ototoxic effects of furosemide.

Previous studies of the effects of ethacrynic acid on the inner ear following intraperitoneal injection of the diuretic have shown a progression of reversible changes occurring in the stria vascularis. The time course of these changes approximately parallels alterations in endolymphatic potential (EP). In this report, some preliminary findings concerning the effects of furosemide after intraperitoneal injection of 80 mg/kg are described. EP declined over a longer time course than that recorded with intravenous injection. Cochlear microphonic (CM) and compound action potential (CAP) also declined but to differing degrees. In the stria vascularis a progression of changes was apparent. In general, the changes were similar to those observed following ethacrynic acid intoxication and affected marginal cells, intermediate cells and strial capillaries. The upper basal turn of the cochlea was affected first and the damage spread apically. In the organ of Corti, stereocilia on the outermost row of outer hair cells were disorganized. This was apparent in approximately the same region as initial strial effects and was only observed when strial derangement was quite marked.

Animals↗
PubMedDate not supplied

Cisplatin ototoxicity involves organ of Corti, stria vascularis and spiral ganglion: modulation by alphaMSH and ORG 2766.

It has been shown that alphaMSH and the nonmelanotropic ACTH/MSH(4-9) analog ORG 2766 can ameliorate cisplatin-induced neurotoxicity and ototoxicity. Here, we investigated whether these peptides delay the occurrence of the cisplatin-induced shift in auditory threshold, and whether they affect the subsequent recovery of cochlear potentials. Chronically implanted round window electrodes were used to obtain daily recordings of auditory nerve compound action potentials (CAP) and cochlear microphonics at frequencies ranging from 2 to 16 kHz. Cisplatin (1.5 mg/kg i.p.) plus alphaMSH, ORG 2766 (75 mug/kg s.c.), or saline were injected daily until the 40-dB CAP threshold shift at 8 kHz was reached. Endocochlear potential (EP) was measured either 1-2 days or 28 days later, followed by morphometric analysis of the cochlea. Peptide cotreatment did not consistently delay the threshold shift; however, the CAP threshold recovered faster and to a greater extent, with the potency order being alphaMSH > ORG 2766 > saline. Significant recovery at the 2 highest frequencies was seen in the alphaMSH-treated animals only. CAP amplitude at high sound pressures, which depends more on nerve function than on outer hair cell (OHC) function, decreased severely in all groups but recovered significantly in the alphaMSH- and completely in the ORG-2766-cotreated group. EP was significantly lower in the first days after the threshold shift but had completely recovered at 28 days. Morphometric analysis of the spiral ganglion also indicated involvement of ganglion cells. OHC loss was most severe in the basal turn of saline-cotreated animals. These data suggest that the cisplatin-induced acute threshold shift might be due to reversible strial failure, whereas subsequent OHC survival determines the final degree of functional recovery. Both OHC loss and neuronal function were ameliorated by peptide cotreatment.

Adrenocorticotropic Hormone↗