Biomedical subjects

S F Klis

Publications and source records attributed to S F Klis.

25 records · Page 2Linked to original sources

PubMed1995

Tetraethylammonium effects on cochlear potentials in the guinea pig.

Voltage-dependent K+ channels in the basolateral membrane of hair cells in guinea-pig cochlea might contribute to the non-linear current-voltage relationships in these hair cells and, thereby, to generation of the extracellular summating potential (SP). To evaluate the role of K+ channels in the generation of the SP the perilymphatic perfusion technique was used to introduce the K(+)-channel blocker tetraethylammonium (TEA) into the cochlea. Sound-evoked cochlear potentials were measured subsequently. Without blocking nerve activity TEA induced reversible shifts of the SP in the negative direction, irrespective of whether we recorded from scala vestibuli or scala tympani. Shifts in the negative direction were probably due to TEA acting directly on the afferent fibres, since removal of nerve activity by the potent Na(+)-channel blocker tetrodotoxin (TTX) prevented TEA from shifting the SP in the negative direction. Once nerve activity had been removed by TTX, administration of TEA caused a small decrease in the magnitude of the SP, both in scala vestibuli and in scala tympani, irrespective of its polarity. The decrease was significant for the highest test frequencies only (8-12 kHz), and completely reversible. The rapidly activated K+ channel in the inner hair cell (IHC) is probably blocked by TEA and this blocking might be responsible for the small decrease in magnitude of the SP. The asymmetric contribution from this K+ channel to the IHC's current-voltage relationship seems to be only partly responsible for the generation of the SP, since blocking of this K+ channel with TEA caused relatively small decreases in the amplitude of the SP. TEA did not affect the endocochlear potential.

Acoustic Stimulation↗

PubMed1994

The effect of nimodipine on cochlear potentials and Na+/K(+)-ATPase activity in normal and hydropic cochleas of the albino guinea pig.

In experimental endolymphatic hydrops (EEH) a decrease in the endocochlear potential (EP) has been reported and is thought to be due to decreased activity of the enzyme Na+/K(+)-ATPase in the stria vascularis. By stimulating Na+/K(+)-ATPase, the EP, and thereby cochlear function as a whole, might be restored. On the other hand, stimulation of stria vascularis Na+/K(+)-ATPase might result in excessive production of endolymph and thus produce or augment hydrops. In this study we have investigated the effect of intraperitoneally applied nimodipine on cochlear potentials and on Na+/K(+)-ATPase activity in the stria vascularis, both in normal cochleas (control) and in cochleas with EEH. Nimodipine is an L-type Ca(2+)-channel blocking agent with Na+/K(+)-ATPase stimulating properties at concentrations as low as 1.5 nM. The compound action potential (CAP), evoked by 2,4 and 8 kHz tone bursts was found to be depressed in the EEH ears with and without nimodipine treatment, and in the nimodipine treated control ears. Statistical analysis (ANOVA) showed that the effects of EEH and nimodipine on the CAP were additive. The negative summating potential (SP), measured extracochlearly at the apex, in response to 4 and 8 kHz tone bursts was significantly enhanced in the EEH ears. Nimodipine treatment did not affect the SP, neither in the control, nor in the EEH ears. Cytochemically, Na+/K(+)-ATPase activity appeared to be decreased in the oedematous stria vascularis of hydropic cochleas. No effect of nimodipine on Na+/K(+)-ATPase activity could be established ultracytochemically, neither in the controls nor in the EEH ears. In the lower turns of some of the nimodipine treated control cochleas a mild hydrops was seen during light-microscopic evaluation. Although it was not possible to prove a stimulatory effect of nimodipine on the enzyme Na+/K(+)-ATPase cytochemically, the finding of mild endolymphatic hydrops in nimodipine treated control ears suggests (a history of) increased endolymph production. This hydrops might be responsible for the depression of the CAP in the nimodipine treated ears.

Animals↗

PubMed1994

Application of a neuroprotective ACTH(4-9) analog to affect cisplatin ototoxicity: an electrocochleographic study in guinea pigs.

Ototoxicity and neurotoxicity are among the most serious side-effects of cisplatin therapy. Previous experiments have shown that neurotoxicity can be delayed or prevented by treatment with the melanocortin-derived peptide ORG 2766, and ACTH4-9 analog. A remedy against ototoxicity is not available. In this study we describe cisplatin-induced abnormalities in cochlear potentials in guinea pigs. These included changes in compound action potential (CAP), cochlear microphonics (CM) and summating potential (SP) at frequencies from 500 Hz to 16 kHz. Cisplatin (2 mg/kg for 8 days) reduced CAP amplitude with the effect becoming more pronounced at higher frequencies. Cisplatin also reduced CM and SP. Concurrent treatment with ORG 2766 prevented cisplatin ototoxicity partially or completely in four out of ten animals. In the other six animals the effects were comparable to those seen in control animals not treated with the peptide. The protective effects found with this neurotrophic peptide warrant further experimentation.

Acoustic Stimulation↗

PubMed1994

Osmotically induced pressure difference in the cochlea and its effect on cochlear potentials.

The electrophysiological effects observed during scala tympani displacements in low-frequency biasing experiments, an increase of the summating potential (SP) together with a decrease of the compound action potential (CAP), correlate well with the effects found in guinea pigs with evoked endolymphatic hydrops. This contributes to the hypothesis that displacement of the basilar membrane underlies the changes found in endolymphatic hydrops. A major difference between both experimental situations is that in low-frequency biasing the basilar membrane is continuously moving, whereas in hydrops the hypothesized displacement would be static. To evaluate the importance of this difference, experiments were performed which attempted to evoke a static displacement of the basilar membrane by perfusing the perilymphatic spaces with perfusates of various osmolalities. Perfusion with hypotonic perfusate (183 mOsm/kg) increased the SP and decreased the CAP (4 kHz stimulation) whereas perfusion with a hypertonic perfusate (397 mOsm/kg) decreased both these potentials. The cochlear microphonics were hardly affected. These data demonstrate that both experimental situations (biasing, i.e. dynamic displacement and osmotic pressure, i.e. static displacement) cause similar changes in the SP and the CAP and the data support the hypothesis that basilar membrane displacement towards scala tympani is an important contributing factor to the electrophysiologic changes in endolymphatic hydrops.

Acoustic Stimulation↗

PubMed1994

Adaptation in the compound action potential response of the guinea pig VIIIth nerve to electric stimulation.

An experimental study, carried out in guinea pigs, was designed to investigate whether forward masking measured psychophysically in 3M-House cochlear implant users might have a correlate in VIIIth nerve activity. The study was based on electrically evoked VIIIth nerve compound action potentials (ECAPs), using a masking paradigm comparable to the one used in the psychophysical study. Trains of 50 maskers with inter-masker-intervals of 509 ms appeared to induce a long-term fatigue effect that could influence the recovery from adaptation measurements. Fatigue stabilized within about 1 to 3 min when masker trains were repeated with intervening silent intervals of 10.5 s. The change in amplitude of probe-evoked ECAPs with increasing masker-probe delays was determined within the steady fatigue state. The recovery-from-adaptation functions obtained from these measurements resembled the forward masking functions found in 3M-House cochlear implant users. No correlate of psychophysical backward masking was found at the VIIIth nerve level. To examine whether hair cells were involved in fatigue and recovery from adaptation, the measurements described above were carried out in intact cochleas and in cochleas without hair cells. Results were essentially the same in the different preparations. The results suggest that processes at the level of the VIIIth nerve could, at least partly, account for forward masking found in 3M-House cochlear implant users. Backward masking must be attributed to mechanisms located centrally to the VIIIth nerve.

Action Potentials↗

PubMed1992

Effects of anoxia on the cochlear summating potential in the guinea pig.

The cochlear summating potential (SP) was recorded extracochlearly from the apex and the round window in 25 guinea pigs, applying anoxia during periods of 1-2 min. For 2 and 8 kHz tone pips at 80 and 60 dB SPL, respectively, the initially negative SP at the apex diminished and even became positive during oxygen cut-off. After restoration of oxygenation, the change in SP reversed direction and was followed by a large negative undershoot. At the round window, the initially positive SP evoked by 8 kHz, 60 dB SPL tone pips followed exactly the same time course, but with inverted polarity, while the majority of the recordings of the initially negative SP evoked by 2 kHz, 80 dB SPL tone pips followed a course similar to the apical negative SP. However, the negative round window SP showed only slight polarity reversal and no undershoot. A small number of the recordings at the round window for 2 kHz showed an increase of the negative SP during anoxia followed by a decline of the SP and recovery after anoxia. The similar time course of the initially negative SP at the apex and the initially positive SP at the round window failed to support the hypothesis of a multi-component SP. However, the polarity reversal during anoxia and the different reactions to anoxia of the 2 kHz round-window SP suggest that the SP may consist of several different components.

Animals↗

PubMed1990

Quantification of the relation between electrophysiologic and morphologic changes in experimental endolymphatic hydrops.

The degree of hydrops in guinea pig ears that had undergone unilateral endolymphatic sac and duct obliteration was quantified. For 15 guinea pigs from a prior study, the correlation between the degree of hydrops and several electrophysiologic measures of the functional state of the cochlea was determined. A significant correlation between the degree of hydrops and a reduction in the low-frequency cochlear microphonic evoked by a 29-Hz tone was found. No correlation was found between the degree of hydrops and the magnitude of the summating potential evoked by 8-kHz probes. A weak correlation was found between the degree of hydrops and a reduction in the compound action potential evoked by 2-kHz probes. Possible differences in the way the endolymphatic duct obliteration exerts its effect on the different cochlear potentials are discussed.

Animals↗