Biomedical subjects

G F Smoorenburg

Publications and source records attributed to G F Smoorenburg.

At least 19 recordsLinked to original sources

PubMed2005

Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement procedure. Recordings were obtained in 96% of these subjects with this standardised procedure. The group results are presented in terms of peak amplitude and latency, slope of the amplitude growth function and ECAP threshold. The effects of aetiological factors and the duration of deafness on the ECAP were also studied. While large intersubject variability and intrasubject variability (across electrodes) were found, results fell within a consistent pattern and a normative range of peak amplitudes and latencies was established. The aetiological factors had little effect on the ECAP characteristics. However, age affected ECAP amplitude and slope of the amplitude growth function significantly; i.e., the amplitude is higher in the lowest age category (15-30 years). Principal component analysis of the ECAP thresholds shows that the thresholds across 5 electrodes can be described by two factors accounting for 92% of the total variance. The two factors represent the overall level of the threshold profiles ('shift') and their slopes across the electrode array ('tilt'). Correlation between these two factors and the same factors describing the T- and C-levels appeared to be moderate, in the range of 0.5-0.6.

Action Potentials↗

PubMed2005

Reduced expression of sialoglycoconjugates in the outer hair cell glycocalyx after systemic aminoglycoside administration.

In this study we investigated the effect of systemic aminoglycoside administration on the expression of sialoglycoconjugates in the outer hair cell (OHC) glycocalyx of the adult guinea pig. Sialoglycoconjugates were visualized by means of ultrastructural lectin cytochemistry, using Limax flavus agglutinin (LFA) and wheat germ agglutinin (WGA) as probes. Labelling densities were determined for the apical membranes (including the stereocilia and stereociliary cross-links) and basolateral membranes of OHCs in the respective (basal, middle and apical) cochlear turns from animals that had been treated with gentamicin or neomycin for 5 or 15 consecutive days. Our results indicate that: (1) sialoglycoconjugate expression in the OHC glycocalyx demonstrates an intracochlear gradient decreasing towards the apical turn; (2) OHCs demonstrate a polarity in sialoglycoconjugate expression, in that the basolateral membranes contain more sialoglycoconjugates per surface area than the apical membranes; (3) aminoglycoside administration results in reduced expression of sialoglycoconjugates in the OHC glycocalyx; in this respect, basal-turn OHCs are more susceptible than those in the middle and apical turns; (4) reduction in sialoglycoconjugate expression after aminoglycoside administration is more prominent in the basolateral membranes; and (5) the difference in ototoxic potencies between gentamicin and neomycin is not reflected at the level of sialoglycoconjugate expression. The present data support our earlier hypothesis that aminoglycosides, already at an early phase of intoxication, interfere with the function of the endoplasmic reticulum and/or the Golgi apparatus, implying that these organelles play a crucial role in the initial phase of aminoglycoside-induced OHC degeneration.

Aminoglycosides↗

PubMed2001

Perilymphatic application of cisplatin over several days in albino guinea pigs: dose-dependency of electrophysiological and morphological effects.

Cisplatin, at 0, 3, 30 or 300 microg/ml in saline, was applied to the scala tympani of the cochlea of guinea pigs via osmotic mini-pumps, operating at a pump rate of 0.5 microl/h. Electrocochleographic recordings were made from an implanted round window electrode. When an electrocochleographic criterion of ototoxicity was reached (40 dB loss in compound action potential (CAP) threshold at 8 kHz), or after 1 week if this criterion was not reached, the animals were sacrificed for light microscopy. A subgroup of animals had endocochlear potentials (EPs) measured prior to sacrifice. Hearing remained stable in the 0 microg/ml control group, but a sudden drop of auditory sensitivity across the whole frequency range was observed in all other groups. It took 1-5 days before the drop occurred, dependent on cisplatin concentration. CAP and cochlear microphonics were lost simultaneously. The EP was severely depressed in the affected animals, suggesting that cisplatin effects on the EP are primary. However, histology revealed an accompanying loss of outer hair cells, primarily in the basal turn. It is concluded that if cisplatin is given until ototoxicity becomes apparent electrophysiologically, then the cochlear pathology from intrascalar cisplatin administration resembles that from daily parenteral administration at 1.5-2.0 mg/kg. The cochlear pathology from the parenteral treatment was greater than that observed with 30 microg/ml pumps, and less than that from 300 microg/ml pumps.

Action Potentials↗

PubMed2001

Simultaneous exposure to ethyl benzene and noise: synergistic effects on outer hair cells.

The effects on hearing of simultaneous exposure to the ototoxic organic solvent ethyl benzene and broad-band noise were evaluated in rats. The effects of three ethyl benzene concentrations (0, 300 or 400 ppm) and three noise levels (95 or 105 dB(lin) SPL or background noise at 65 dB(lin) SPL) and all their combinations were investigated for a 5 day exposure at 8 h/day. Distortion product otoacoustic emissions and compound action potentials were affected after 105 dB noise alone, and after 105 dB noise in combination with ethyl benzene (300 and 400 ppm). However, the amount of loss for these combinations did not exceed the loss for 105 dB noise alone. Outer hair cell (OHC) loss after exposure to 300 ppm ethyl benzene was located in the third row of OHCs. At 400 ppm, the loss spread out to the second and first row of OHCs. Noise alone hardly affected the OHC counts except for a minor loss in the first row of OHCs after 105 dB SPL. Noise at 105 dB in combination with ethyl benzene at 300 and 400 ppm, however, showed OHC loss greater than the sum of the losses induced by noise and ethyl benzene alone.

Action Potentials↗

PubMed2001

Summating potential in the guinea pig cochlea after perilymphatic perfusion with arginine-vasopressin.

We hypothesized that arginine-vasopressin (AVP), the natural vasopressin in the guinea pig, might increase the cochlear summating potential, indicating an increase in endolymphatic volume. Guinea pig cochleas were perfused with artificial perilymph for 15 min, with or without AVP (2 x 10(-6) M). In 1 group of animals, summating potentials (SP), compound action potentials and cochlear microphonics evoked by 2, 4 and 8 kHz tone bursts were measured with an apically placed electrode 15 min, 1 and 2 h after perilymphatic perfusion. In another group of animals the SP and endocochlear potential (EP) were measured simultaneously in the scala media during and after perfusion. In both groups the SP had increased significantly 15 min after perfusion with AVP and this increase was reversible. At the concentration of AVP used the increase in SP was not related to EP alterations. On light microscopic examination of the cochlea no evident increase in scala media volume could be detected. The increase in the SP (a sensitive indicator of acute endolymphatic hydrops) after perfusion with AVP suggests that this neuropeptide plays a role in the regulation of the ion and fluid balance in the cochlea.

Action Potentials↗

PubMed2000

Reversible cisplatin ototoxicity in the albino guinea pig.

Guinea pigs implanted with round window electrodes received daily doses (2.0 mg/kg) of cisplatin until a profound hearing loss occurred (> 40 dB at 8 kHz). Afterwards, pronounced recovery occurred. Recovery progressed over intervals up to 3 weeks before it saturated. Loss and recovery involved both the compound action potential and, less pronounced, the cochlear microphonics. Cochlear potentials evoked by lower frequencies recovered more fully than those evoked by higher frequencies. Loss and recovery was found also in the endocochlear potential. Outer hair cell counts did not change over the recovery period. These findings confirm our previously reported results on the reversibility of cisplatin damage. Further, they implicate the vascular stria as an important target for cisplatin in the cochlea.

Action Potentials↗

PubMed2000

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

Action Potentials↗

PubMed2000

The rat cochlea in the absence of circulating adrenal hormones: an electrophysiological and morphological study.

Circulating adrenal hormones affect strial function. Removal of endogenous levels of adrenal steroids by bilateral adrenalectomy (ADX) in rats causes a decrease of Na(+)/K(+)-ATPase activity in the cochlear lateral wall [Rarey et al., 1989. Arch. Otolaryngol. Head Neck Surg. 115, 817-821] and a decrease of the volume of the marginal cells in the stria vascularis [Lohuis et al., 1990. Acta Otolaryngol. (Stockh.) 110, 348-356]. To study further the effect of absence of circulating adrenocorticosteroids on cochlear function, 18 male Long Evans rats underwent either an ADX or a SHAM operation. Electrocochleography was performed 1 week after surgery for tone bursts in a frequency range of 1-16 kHz. Thereafter, the cochleas were harvested and examined histologically. No significant changes in the amplitude growth curves of the summating potential (SP), the compound action potential (CAP) and the cochlear microphonics (CM) were detected after ADX. However, visually, there appeared to be a decrease of endolymphatic volume (tentatively called imdrops). Reissner's membrane (RM) extended less into scala vestibuli in ADX animals than in SHAM-operated animals. The ratio between the length of RM and the straight distance between the medial and lateral attachment points of RM were used as an objective measure to quantify this effect in each sub-apical half turn of the cochlea. The decrease in length of RM was statistically significant. Thus, circulating adrenal hormones appear to be necessary for normal cochlear fluid homeostasis. Absence of one or more of these hormones leads to shrinkage of the scala media (imdrops). However, the absence of adrenal hormones does not affect the gross cochlear potentials. Apparently, the cochlea is capable of compensating for the absence of circulating adrenal hormones to sustain the conditions necessary for proper cochlear transduction.

Action Potentials↗

PubMed2000

Dose-dependent effect of 8-day cisplatin administration upon the morphology of the albino guinea pig cochlea.

Numerous studies investigating cisplatin ototoxicity in animals have been performed, but it is difficult to derive a clear dose-effect relation from these studies. The degree of cisplatin-induced ototoxicity depends on a multitude of factors. Many parameters, such as dose, mode of administration, dosage schedule and concomitant administration of protective additives, vary among the published studies. Therefore, we performed a basic dose-effect study on cisplatin ototoxicity in the guinea pig. Albino guinea pigs were treated with cisplatin at daily doses of either 0.7, 1.0, 1.25, 1.5 or 2.0 mg/kg for 8 consecutive days. Electrocochleography was performed on day 10 after which the cochleas were removed and processed for histological examination. The electrophysiological results showed a marked transition from almost no ototoxic effect to a large effect between a daily dose of 1.25 and 1.5 mg/kg (Stengs et al., 1998). Outer hair cell (OHC) counts corresponded well with the electrophysiological results. At daily doses of 0.7, 1.0 and 1.25 mg/kg no statistically significant OHC loss was observed, whereas OHC loss averaged 60% and 65% in the basal turns at daily doses of 1. 5 and 2.0 mg/kg, respectively. Morphological changes in the stria vascularis were present only in cochleas from animals treated with cisplatin doses of 1.0, 1.25 and 1.5 mg/kg/day. Cochleas from animals treated with a daily cisplatin dose of 2.0 mg/kg for 8 consecutive days showed an endolymphatic hydrops. The present study shows that cisplatin, administered at a daily dose of 1.5 mg/kg for 8 consecutive days, provides a degree of OHC loss that is well suited to study the effects of putative protective agents and possible hair cell recovery.

Animals↗

PubMed2000

Cisplatin-induced ototoxicity: morphological evidence of spontaneous outer hair cell recovery in albino guinea pigs?

Cisplatin is frequently used in the treatment of various forms of malignancies. Its therapeutic efficacy, however, is limited by the occurrence of sensorineural hearing loss. Little is known about the course of hearing loss over longer time intervals after cessation of cisplatin administration. Infrequently, recovery of hearing has been described in animals and humans. Stengs et al. (1997) treated guinea pigs with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days and subsequently studied cochlear function after survival times varying from 1 day to 16 weeks. Spontaneous improvement of the hair cell-related potentials (cochlear microphonics and summating potentials) was observed starting 2 weeks after cessation of treatment. In the present study we examined light microscopically the cochleas used in the study of Stengs et al. (1997). One day after cessation of cisplatin administration outer hair cell (OHC) loss in the basal cochlear turn averaged 66%. In the 1-week survival group, OHC counts were similar to those of the 1-day survival group. In the 4-week survival group, however, a relatively small loss of OHCs was found in the basal cochlear turn; OHC loss averaged only 15%. A similar loss was found after 8 weeks. In the 16-week survival group, OHC loss in the basal turn increased to 48%, but this was not statistically significant. Our histological observations are in line with the electrophysiological data from the same animals. Our findings suggest that OHCs recover from cisplatin-induced damage 1-4 weeks after treatment. However, the results do not allow a conclusion as to whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs.

Animals↗

PubMed2000

Histological effects of co-administration of an ACTH((4-9)) analogue, ORG 2766, on cisplatin ototoxicity in the albino guinea pig.

Cisplatin is one of the most potent antineoplastic drugs presently known, but its therapeutic efficacy is seriously limited by several side effects such as ototoxicity. Several compounds that are known for their nephroprotective effects also seem to reduce the incidence and severity of cisplatin-induced ototoxicity. Hamers et al. (1994) and De Groot et al. (1997) investigated the possibly protective effect of concomitant administration of the ACTH((4-9)) analogue ORG 2766 upon cisplatin ototoxicity in guinea pigs. Animals were treated with cisplatin at a daily dose of 2.0 mg/kg for 8 consecutive days and ORG 2766 at a daily dose of 75 mcg/kg for 9 days. Concomitant administration of cisplatin plus ORG 2766 resulted in a bimodal distribution of the electrophysiological data (compound action potential and cochlear microphonics amplitudes) and the histological data (outer hair cell (OHC) counts). It was surmised that this dichotomy might occur at a certain cisplatin dose. We investigated whether this protective effect of ORG 2766 could be enhanced by reducing the daily dose of cisplatin while maintaining the same dose of ORG 2766. Thirty-six animals were treated with daily i.p. injections of cisplatin at a dose of 1.0 mg/kg (n=18) or 1.5 mg/kg (n=18) for 8 consecutive days. When comparing the mean OHC counts of the different experimental groups, treatment with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days resulted in a considerable loss of OHCs, which was significantly reduced after co-administration of ORG 2766. Co-treatment with ORG 2766 did not result in a change in the volume of the scala media. The present results are in agreement with the electrophysiological results published earlier (Stengs et al., 1998b).

Adrenocorticotropic Hormone↗

PubMed2000

Experimental autoimmune inner ear disease: an electrocochleographic and histophysiologic study.

Systemic immunization with swine inner ear antigens in complete Freund's adjuvant induces functional disturbances in the cochlea. Morphometric data indicate that an endolymphatic hydrops develops within 2 weeks. It diminishes 6 weeks after immunization. A progressive decrease in the compound action potential amplitude is observed from 2 to 6 weeks after immunization. Enhancement of the amplitude of the summating potential is present without a clear overall correlation to the presence of endolymphatic hydrops. The amplitude of the cochlear microphonics shows no significant changes after immunization. Western blot analysis of the sera performed 2 and 6 weeks after immunization shows enhanced reactivity at 68, 50, 45, and 27 kd molecular weights, as compared to controls. The same spectrum of cross-reacting antibodies is believed to be instrumental in immune-mediated sensorineural hearing loss in patients. Apparently, cross-reacting antibodies and released mediators disturb cochlear homeostasis, resulting in the observed changes in the electrophysiological responses. However, these changes are not clearly related to structural changes at the light and electron microscopic levels.

Animals↗

PubMed1999

Protection and spontaneous recovery from cisplatin-induced hearing loss.

Cisplatin [cis-diamminechloroplatinum(II)] has proved itself as a potent antineoplastic agent. However, nephrotoxicity, neurotoxicity, gastrointestinal toxicity, myelosuppression, and ototoxicity interfere with its therapeutical efficacy. Forced diuresis reduces nephrotoxicity, effectively leaving neurotoxicity and ototoxicity as the major side effects of concern, and gastrointestinal toxicity and myelosuppression as the secondary side effects. So far, attempts to reduce these side effects by developing equally potent platinum analogs have been unsuccessful. Some success has been achieved, however, by co-treatment with protective agents. Nearly all these agents are sulfur- or sulfhydryl-containing compounds (thio compounds), known as antioxidants and potent heavy metal chelators. These thio compounds may provide protection from cisplatin toxicity either (1) by direct interaction between the cisplatin and the thio moiety, (2) by displacing platinum from its site of toxic action, (3) by preventing platinum from interfering with superoxide dismutase, or (4) by scavenging of cisplatin-induced free radicals. In particular the first two protective mechanisms bear the risk of reducing the antineoplastic activity of cisplatin. Since nephrotoxicity can be controlled effectively by forced diuresis, a more specific approach of coping with ototoxicity by focusing on protection at the sensorineural level was chosen. Being familiar with the neuro-protective and neurotrophic properties of ACTH-related neuropeptides, specifically against cisplatin-induced peripheral neuropathies, it was judged expedient to test for a possible otoprotective action of these neuropeptides. The results were positive, although tainted with high interanimal variability. When testing for the possibility that the neuropeptides would merely delay cisplatin-induced ototoxicity rather than reduce it, it was discovered in control series without neuropeptide co-treatment that the ear can recover spontaneously from cisplatin-induced hearing loss. This was found both electrophysiologically and in outer hair cell (OHC) counts. Although these preliminary findings require further investigation, they strongly suggest that spontaneous recovery of cochlear injury can occur in the mature mammalian cochlea. Moreover, the otoprotective action of the ACTH-related neuropeptides suggests that it may be possible to stimulate recovery from acute hearing loss using neuropeptides.

Action Potentials↗

PubMed1999

Cisplatin ototoxicity and the possibly protective effect of alpha-melanocyte stimulating hormone.

It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so-called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our group has found that cisplatin-induced ototoxicity can also be reduced or prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766 (Hamers et al., 1994; De Groot et al., 1997). The present study was designed to investigate the possibly ameliorating effects of the physiologically more relevant naturally occurring neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) upon cisplatin ototoxicity and to compare its protective effects to those of ORG 2766. For eight consecutive days guinea pigs were treated with cisplatin at a concentration of either 1.5 mg/kg/day or 2 mg/kg/day. Animals were co-treated with either alpha-MSH (75 microg/kg/day), ORG 2766 (75 microg/kg/day), or a sham injection containing physiological saline. Electrocochleography and hair cell counts were performed. Treatment with 1.5 mg/kg/day cisplatin resulted in a large variability of the morphological and electrophysiological data, a variability that might have masked possible effects of ORG 2766 and alpha-MSH. Treatment with 2 mg/kg/day cisplatin caused less variable, severe reductions in the compound action potentials and cochlear microphonics combined with basal and middle-turn outer hair cell loss in five out of six animals. However, in the alpha-MSH co-treated groups, two out of six animals could be classified as normal, two animals as moderately affected and two animals as severely affected. In the ORG 2766 co-treated group we found three animals that were not affected and three animals that were severely affected. We conclude that the protective effects of alpha-MSH and ORG 2766 co-treatment are comparable and that alpha-MSH might be clinically useful in protecting against cisplatin-induced ototoxicity.

Action Potentials↗

PubMed1999

Signs of endolymphatic hydrops after perilymphatic perfusion of the guinea pig cochlea with cholera toxin; a pharmacological model of acute endolymphatic hydrops.

There are indications that endolymph homeostasis is controlled by intracellular cAMP levels in cells surrounding the scala media. Cholera toxin is a potent stimulator of adenylate cyclase, i.e. it increases cAMP levels. We hypothesized that perilymphatic perfusion of cholera toxin might increase endolymph volume by stimulating adenylate cyclase activity, providing us with a pharmacological model of acute endolymphatic hydrops (EH). Guinea pig cochleas were perfused with artificial perilymph (15 min), with or without cholera toxin (10 microg/ml). The endocochlear potential (EP) was measured during and after perfusion. The summating potential (SP), evoked by 2, 4 and 8 kHz tone bursts, was measured via an apically placed electrode 0, 1, 2, 3 and 4 h after perfusion. Thereafter, the cochleas were fixed to enable measurement of the length of Reissner's membrane, reflecting EH. After perfusion the EP increased significantly over time in the cholera toxin group as compared to the controls. Also, the SP increased gradually at all frequencies in the cholera toxin group. Comparison within animals showed that the increase in SP became significant after 2 h at 4 kHz, after 3 h at 2 kHz and after 4 h at 8 kHz. In the control group the SP did not change significantly. The compound action potential (CAP) amplitude decreased monotonically over time at all frequencies in both the cholera toxin group and the control group, but it decreased faster in the cholera toxin group. Also, the cochlear microphonics amplitude decreased over time at all frequencies in both groups, but the decrease was significant only in the cholera toxin group after 3 h at 2 and 4 kHz. Quantification of the length of Reissner's membrane showed a small but insignificant enlargement in the cholera toxin treated animals compared to controls. These results are in accord with our view that EH is accompanied by an increase in SP and a decrease in CAP. Our results partially confirm previous results of Feldman and Brusilow (Proc. Natl. Acad. Sci. USA (1973) 73, 1761-1764). New aspects in relation to that study are the significantly increased EP and SP. In the classical EH model, based on obstruction of the absorptive function of the endolymphatic sac, increased SPs are accompanied by decreased EPs. In this cholera toxin model of EH, it is unlikely that the endolymphatic sac is involved. Apparently, EH can be based on mechanisms located in the cochlea itself as opposed to mechanisms located in the endolymphatic sac.

Animals↗

PubMed1999

The ototoxic effects of ethyl benzene in rats.

Exposure to organic solvents has been shown to be ototoxic in animals and there is evidence that these solvents can induce hearing loss in humans. In this study, the effects of inhalation of the possibly ototoxic solvent ethyl benzene on the cochlear function and morphology were evaluated using three complementary techniques: (1) reflex modification audiometry (RMA), (2) electrocochleography and (3) histological examination of the cochleas. Rats were exposed to either ethyl benzene (800 ppm, 8 h/day for 5 days) or to control conditions. The RMA threshold increased significantly by about 25 dB, 1 and 4 weeks after the exposure, irrespective of the stimulus frequency tested (4-24 kHz). Electrocochleography was performed between 8 and 11 weeks after exposure to the organic solvent. The threshold for the compound action potential increased significantly by 10-30 dB at all frequencies tested (1-24 kHz). Histological examination of the cochlea showed outer hair cell (OHC) loss, especially in the upper basal and lower middle turns (corresponding to the mid-frequency region) to an extent of 65%. We conclude that exposure to 800 ppm ethyl benzene for 8 h/day during 5 days induces hearing loss in rats due to OHC loss.

Administration, Inhalation↗

PubMed1998

The generation of DC potentials in a computational model of the organ of Corti: effects of voltage-dependent K+ channels in the basolateral membrane of the inner hair cell.

A computational model of the organ of Corti is described to assist in the interpretation of electrophysiological data concerning the role of the K+ channels residing in the basolateral membrane of cochlear hair cells. Recent in vivo data from Van Emst et al. (Hear. Res. 88, 27-35 (1995); Hear. Res. 102, 70-80 (1996)) about the effects of selective blocking of K+ channels indicate that these channels affect the magnitude of the summating potential. In order to understand the nature of this effect, the model of Dallos (Hear. Res. 14, 281-291 (1984)) was extended to account for the voltage- and time-dependent properties of the K+ channels in the basolateral membrane of the inner hair cell (IHC) (Kros and Crawford, J. Physiol. 421, 262-291 (1990)). The model shows that the K+ channels induce a shift in the mean IHC basolateral conductance when high-frequency stimuli are present. As a result, cochlear transduction shifts to a different electrical operating state and this is the source of a marked decrease in the stimulus-evoked DC response of the IHC. Extracellularly, in contrast, the magnitude of the DC response increases slightly. At low frequencies, the K+ channels respond to the stimulus waveform on a cycle-by-cycle basis. The waveform distortion associated with this dynamic basolateral impedance induces a further decrease in the intracellular stimulus-evoked DC response of the IHC. Thus, K+ channels in the IHC appear to be directly involved in the generation of the DC receptor potential at low frequencies, but at high frequencies they simply modify the size of the DC response.

Acoustic Stimulation↗

PubMed1998

Induction of endolymphatic hydrops in the guinea pig by perisaccular deposition of sepharose beads carrying and not carrying immune complexes.

We tried to induce endolymphatic hydrops in guinea pig cochleas by unilateral, perisaccular deposition of sepharose beads carrying immune complexes. Controls consisted of the deposition of sepharose beads without immune complexes and the contralateral, untreated ear. The effects of the treatment were studied by light microscopy and electrophysiological recordings of the gross cochlear potentials 1, 2, and 6 weeks after treatment. Each condition included six animals. Analysis of variance of the morphometric data concerning the ears treated with deposition of the beads showed a statistically significant difference (P = 0.04) between the degree of hydrops found for the beads with immune complexes and for those without. The difference between the treated ears and the contralateral untreated ears was significant (P = 0.01) for the beads with immune complexes and not significant (P = 0.8) for those without immune complexes while there was no significant effect of post-treatment time interval. Analysis of variance of the electrophysiological data, collected in response to tone bursts at the apex of the cochlea, showed no significant differences between the results for the beads with and without immune complexes. Therefore these results were pooled. One week after treatment the pooled results for the compound action potential showed a small decrease in amplitude, just significant at 2 kHz, but not at 4 and 8 kHz. This decrease disappeared completely after 6 weeks. The pooled results for the negative summating potential (SP) showed a significant increase in magnitude at all frequencies decreasing with post-treatment interval. The cochlear microphonics did not demonstrate any change in amplitude after treatment. The results indicate that deposition of sepharose beads with immune complexes induces endolymphatic hydrops. Also, deposition of the sepharose beads itself may have induced hydrops together with enhancement of the SP. SP enhancement may be related to the development of endolymphatic hydrops rather than to the presence of hydrops as such. This may be based on pressure build-up while hydrops develops.

Action Potentials↗