Desmond L. Kirk

Microphonic and DPOAE measurements suggest a micromechanical mechanism for the ‘bounce’ phenomenon following low-frequency tones

Neural auditory thresholds in the guinea pig can be temporarily improved by up to 6 dB about 2 min after the cessation of an moderately intense low-frequency tone (Kirk and Patuzzi, 1997). We have measured changes in the f2-f1 distortion product otoacoustic emission (DPOAE) and low-frequency microphonic potential in scala tympani before, during and after a low-frequency tone (200 Hz) to determine the cause of this so-called bounce phenomenon. In particular we have analysed the low-frequency microphonic waveform in detail to estimate changes in the maximal receptor current through the outer hair cells (OHCs), the sensitivity of the OHC forward transduction process and the change in OHC operating point on the mechano-electrical transduction transfer curve. Our results indicate that a 200 Hz tone changes the maximal current and sensitivity of the OHCs minimally, but more importantly, it transiently changes the operating point on the OHC transfer curve. In particular, the operating point changes are consistent with a movement of the OHC stereocilia away from the OHC basal body at the peak of the bounce. These changes detected using the microphonic potential are associated with changes in the level of the f2-f1 DPOAE that correlate well with the electrical measurements. We suggest that the shift in operating point is largely responsible for the increase in cochlear sensitivity, and is due to a disruption of the salt balance within the cochlea during the intense low-frequency tone.

Modulation of −: Evidence for a GABA-ergic efferent system in apical cochlea of the guinea pig

f2-f1, but not 2f1-f2, was reduced in amplitude during continuous stimulation of the test ear with the primary tones, and with single tones near the primary frequencies. Stimulation of the contralateral ear, either with broad band noise or with single tones near the primary frequencies, also reduced f2-f1. Ipsilateral and contralateral effects were additive and were restricted to the frequency range between about 2 kHz and 7 kHz. Contralateral, but not ipsilateral suppression, was blocked after systemic administration of strychnine. Ipsilateral suppression was eliminated by perfusion of the cochlea with tetrodotoxin. Both contralateral and ipsilateral suppression were abolished after perfusion of the cochlea with bicuculline. The results are evidence for a role for a GABA-ergic efferent system in the modulation of outer hair cell mechanics in the apical cochlea.

Changes to low-frequency components of the TEOAE following acoustic trauma to the base of the cochlea

Several studies have shown that acoustic trauma to the base of the cochlea can result in loss of transient-evoked otoacoustic emission (TEOAE) energy at frequencies much lower than those affected in the audiogram. We have extended these studies to show that the low-frequency emission energy was substantially affected if the transient stimulus included frequencies within the range affected by the trauma, otherwise the change observed was small. In keeping with the suggestion that TEOAEs are predominantly comprised of intermodulation distortion energy (Yates and Withnell, Hear. Res. 136 (1999) 49-64), trauma to the basal region of the cochlea was found to affect emission energy across a broad frequency range in response to a wide-band acoustic stimulus. Further, group delay measurements demonstrated that the dominant contribution to the TEOAE originated from the basal region of the cochlea.

Frequency tuning and acoustic enhancement of electrically evoked otoacoustic emissions in the guinea pig cochlea

Electrically evoked otoacoustic emissions (EEOAEs) were generated by ac stimulation in scala media of turns 1, 2, and 3 in the guinea pig cochlea. In each turn EEOAEs were recorded at frequencies up to and slightly above the estimated characteristic frequency (CF) of the stimulation site. Acoustic enhancement of EEOAEs was present at all emission frequencies in turns 2 and 3 but could be demonstrated in turn 1 only at emission frequencies that fell within a notch in the EEOAE tuning function. There was no evidence, in any turn, of a transition from enhancement to suppression as the emission frequency approached the CF of the stimulation site. The results were not consistent with the hypothesis [D. C. Mountain and A. E. Hubbard, Hear, Res. 42, 195-202 (1989)] that acoustic enhancement results from a reduction in the effectiveness of forward transduction in a negative feedback loop.

Otoacoustic emissions measured with a physically open recording system

Otoacoustic emissions have historically been measured with an acoustical probe assembly hermetically sealed in the ear canal, imposing in most cases a limited stimulus bandwidth. A physically open recording system should afford the possibility of a greater stimulus bandwidth but the change in acoustical load may affect the magnitude of otoacoustic emissions obtained. Here it is reported that the authors have measured in the guinea pig transient-evoked otoacoustic emissions extending in frequency to 20 kHz and cubic distortion tone otoacoustic emissions for f2 = 4737 and 8096 Hz with a physically open sound system. To address the effect of acoustical load provided by a physically open versus hermetically sealed system, the authors compared the amplitude of electrically evoked otoacoustic emissions recorded from a guinea pig in each case. The change in acoustical load in the ear canal introduced by the change in recording setup did not appear to make a substantial difference to the magnitude of otoacoustic emissions measured. A physically open recording system provides a good alternative to traditional acoustical probe assemblies sealed in the ear canal for the laboratory measurement of acoustically evoked otoacoustic emissions, with the advantage of permitting a greater stimulus bandwidth.

4-Aminopyridine in Scala media Reversibly Alters the Cochlear Potentials and Suppresses Electrically Evoked Oto-Acoustic Emissions

Iontophoresis of 4-aminopyridine into scala media of the guinea pig cochlea caused elevation of the thresholds of the compound action potential of the auditory nerve, loss of amplitude of the extracellular cochlear microphonic response (CM), increase in the endocochlear potential (EP) and reduction in the amplitude of electrically evoked oto-acoustic emissions (EEOAEs). These changes were reversible over 10–20 min. The reciprocity of the changes in the CM and the EP was consistent with an interruption of both DC and AC currents through outer hair cells (OHCs), probably by blockade of mechano-electrical transduction (MET) channels in OHCs. Reductions in EEOAEs were consistent with the extrinsically applied generating current entering the OHC via the MET channels. Implications for the activation of OHC electro-motility in vivo are discussed.

Effects of 4-aminopyridine on electrically evoked cochlear emissions and mechano-transduction in guinea pig outer hair cells

Stimulation of the cochlea with alternating current produces sound in the ear canal. These electrically evoked oto-acoustic emissions (EEOAEs) are attributed to electro-motility of outer hair cells (OHCs). Earlier work suggested EEOAEs were sensitive to the open probability of OHC mechano-electrical transduction (MET) channels. They were attenuated by 4-aminopyridine (4-AP) and amplitude-modulated by low frequency sound, consistent with current gaining access to a motility source via the MET conductance. However, inconsistencies in the behaviour as well as physical considerations argued against this simple interpretation. In this study the behaviour of EEOAEs in the presence of 4-AP in scala media was examined along with OHC transfer functions derived from low frequency cochlear microphonic (CM) waveforms. Both the level and the modulation of the EEOAEs were reduced by 4-AP, but disproportionately more so than the 4-AP-induced loss of CM. In addition, the modulation as well as the level of the EEOAEs recovered more rapidly than the CM. Both these results indicated that 4-AP modified the process of EEOAE generation independently of its effect on the gross receptor current through the MET conductance. Changes in the derived OHC transfer functions, specifically shifts in the estimated operating bias of the MET channels, indicated the effects of 4-AP applied to the endolymphatic surface of OHCs were complex. It is suggested that both direct and indirect consequences of a 4-AP blockade may have contributed. 4-AP was ineffective when applied to scala tympani.

Does BAPTA leave outer hair cell transduction channels closed

The calcium chelator BAPTA was iontophoresed into the scala media of the second turn of the guinea pig cochlea. This produced a reduction in low frequency cochlear microphonic (CM) measured in scala media and an elevation of the cochlear action potential (CAP) threshold that lasted for the duration of the experiment. Using two pipettes, one filled with KCl and the other KCl and BAPTA (50, 20 and 5 mM) it was possible to observe the effect of passing current through one electrode while measuring the endolymphatic potential (EP) with the other. The results demonstrated that current passed via the BAPTA pipette caused a sustained increase in EP of 8.2, 12.9 and 7.8 mV in the three animals used. This increase coincided with the decrease in low frequency CM that indicated a causal connection between the two. In a second series of experiments, pipettes with larger tips were inserted into scala media in the first cochlear turn and BAPTA was allowed to diffuse from the pipette. The results confirmed the relationship between EP increase and the fall of scala media CM. One interpretation of these results is that lowering the Ca2+ concentration of endolymph with BAPTA inhibits mechano-electrical transduction in outer hair cells (OHCs) and leaves the hair cell transduction channels in a closed state, thus increasing the resistance across OHCs and increasing the EP. These findings are consistent with a model of hair cell transduction in which tension on stereo cilia opens the transduction channels.