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R Patuzzi

Publications and source records attributed to R Patuzzi.

At least 19 recordsLinked to original sources
PubMed2007

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.

Action Potentials↗
PubMed2005

The effect of BAPTA and 4AP in scala media on transduction and cochlear gain.

We have injected by iontophoresis 4-amino-pyridine, a K+ channel blocker and BAPTA, (a Ca++ chelator), into scala media of the first three turns of the guinea pig cochlea. We measured the reduction in outer hair cell (OHC) receptor current, as indicated by cochlear microphonic measured in scala media evoked by a 207 Hz tone, and compared this with the elevation of the cochlear action potential (CAP) threshold. We found that in the basal turn, for frequencies between 12 and 21 kHz, CAP threshold was elevated by about 30 dB, while in the second turn, at the 3 kHz place, the maximum elevation was 15 dB. In the third turn, iontophoresis of 4AP and BAPTA reduced CM by similar amounts to that in the basal and second turn, but caused negligible elevation of CAP threshold. We conclude that the gain of the cochlear amplifier is maximal for basal turn frequencies, is halved at 3 kHz, and is reduced to close to one for frequencies below 1 kHz (no active gain). The effect of 4AP and BAPTA on neural threshold and the receptor current represented by CM may be explained by their action on OHC transduction without the involvement of IHCs.

4-Aminopyridine↗
PubMed2004

Effects of a calcium channel blocker on spontaneous neural noise and gross action potential waveforms in the guinea pig cochlea.

The effects of the L-type Ca2+ channel blocker nimodipine on the spectrum of the spontaneous neural noise (SNN) and the waveform of the gross sound-evoked compound action potential (CAP) were investigated by perilymphatic perfusion in the guinea pig cochlea. Both the SNN and the CAP were reversibly suppressed by nimodipine. The percentage reduction in SNN was dose-dependent in a manner very similar to the results obtained with the measures of CAP threshold changes. The reduction in the peak SNN caused by 10 microM nimodipine was the same as that caused by 500 microM kainic acid, which totally eliminated any neural responses. For 1 microM nimodipine there was an apparent dissociation between the SNN and CAP changes such that the SNN could be markedly suppressed with only very small changes in CAP thresholds. These results imply that spontaneous release of neurotransmitter from the inner hair cell is more sensitive to block of calcium channels than evoked release. There was no evidence for any marked shift caused by nimodipine, in the position of the main (900 Hz) spectral peak in the SNN. Comparison of the CAP waveform before and after nimodipine perfusion showed that the CAP waveforms were unchanged despite the change in sensitivity. These data do not support the notion of any significant postsynaptic site of action of nimodipine. The data hence provide further support for an exclusively presynaptic role for L-type Ca2+ channels in the regulation of both evoked and spontaneous neurotransmitter release from inner hair cells.

Action Potentials↗
PubMed1999

The continuing search for outer hair cell afferents in the guinea pig spiral ganglion.

Antidromic stimulation of the stump of the VIIIth nerve was combined with microelectrode recording in the spiral ganglion of the guinea pig cochlea in an attempt to identify a sub-population of neurons with long-latency antidromic action potentials that might correspond to the thin unmyelinated afferent neurons emanating from the outer hair cells. The techniques used were similar but not identical to those employed in an earlier study by Brown (1994). By far the largest population of cells contacted had short antidromic latencies (0.58+/-0.12 ms, 76 units) and also responded to acoustic stimulation. These were assumed to be type I afferents emanating from inner hair cells. Eight cells had antidromic latencies larger than 1 ms, all but one of which had a zero spontaneous rate. All eight of these longer-latency cells were unresponsive to acoustic stimulation despite the fact that short-latency neurons in the same cochleas showed robust responses to sound before and after they were contacted. Four of these longer-latency cells had their antidromic thresholds accurately measured and two had significantly higher thresholds to electrical stimulation (0.1 ms duration) than type I cells in the same animal while two had similar electrical thresholds. Attempts to trace the eight long-latency neurons to the outer hair cells using intracellular injection of horseradish peroxidase were unsuccessful. On the basis of present evidence, we cannot conclude definitively that the long-latency neurons found in the spiral ganglion belong to the outer hair cell afferent population.

Animals↗
PubMed1998

The Goldman-Hodgkin-Katz equation and graphical 'load-line' analysis of ionic flow through outer hair cells.

While the 'membrane potential' of a cell which has a homogeneous membrane and surrounding environment, and which is not pumping ions electrogenically (passing no net current through its membranes), can be estimated from the Goldman voltage equation, this equation is inappropriate for other cells. In the mammalian cochlea such problematic cells include the cells of stria vascularis and the sensory hair cells of the organ of Corti. Not only is the Goldman voltage equation inappropriate, but in asymmetric cells the concept of a single 'membrane potential' is misleading: a different transmembrane voltage is required to define the electrical state of each section of the cell's heterogeneous membrane. This paper presents a graphical 'load-line analysis' of currents through one such asymmetric cell, the outer hair cells of the organ of Corti. The approach is extremely useful in discussing the effects of various cochlear manipulations on the electrical potential within hair cells, even without a detailed knowledge of their membrane conductance. The paper discusses how modified Goldman-Hodgkin-Katz equations can be used to describe stretch-activated channels, voltage-controlled channels, ligand-mediated channels, and how the combination of these channels and the extracellular ionic concentrations should affect the hair cell's resting intracellular potential and resting transcellular current, its receptor current and receptor potential, and the extracellular microphonic potential around these cells. Two other issues discussed are the role of voltage-controlled channels in genetically determining membrane potential, and the insensitivity of hair cells to changes of extracellular potassium concentration under some conditions.

Acoustic Stimulation↗
PubMed1998

Automatic monitoring of mechano-electrical transduction in the guinea pig cochlea.

We have estimated the transfer curve relating instantaneous sound pressure in the ear canal to instantaneous receptor current through the outer hair cells (OHCs) in the basal turn of the guinea pig cochlea using the cochlear microphonic (CM) elicited by continuous 200 Hz tones. The transfer curve is well approximated by a Boltzmann activation curve which has been automatically analysed using a custom-built electronic circuit which continuously derives the three parameters defining the curve with a time resolution of seconds. This technique offers a convenient method of monitoring changes in OHC mechano-electrical transduction due to cochlear disturbances, and allows the investigation of cochlear homeostasis over the course of hours. We present here details of the technique, evidence that the recordings are minimally contaminated by neural responses, and normative data on the changes in the parameters with sound level. As the level of the 200 Hz tone increases, the equivalent operating point on the transfer curve migrates in a way consistent with a movement of the organ of Corti towards scala tympani or a contraction of the outer hair cells. Surprisingly, the effective slope of the curve which represents the mechanical sensitivity of the transduction process decreases over an 8 to 1 range as the level of the 200 Hz tone is increased. The effect of this variation is that the amplitude of the equivalent mechanical displacement input to the mechano-electrical transduction process appears to increase by a mere 2 to 1 while the sound level increases by a factor of 20 to 1. These changes are not neurally mediated, since they also occur in the presence of tetrodotoxin and the blocker of afferent neurotransmission, kainate.

Acoustic Stimulation↗
PubMed1998

Exponential onset and recovery of temporary threshold shift after loud sound: evidence for long-term inactivation of mechano-electrical transduction channels.

The onset and recovery of temporary threshold shift (TTS) in one human subject (the author) has been studied during and after pure-tone overstimulation lasting between minutes and days. Under the conditions of these experiments the time courses appeared reproducible, and thresholds always recovered to normal within 3 days. The onset and recovery followed a multiple-exponential time course, with the time constants for the onset being 6.5 and 800 min, and the recovery time constants being 30, 240 and 800 min. The observed time courses were consistent with data previously reported in humans, and with the view that the threshold elevation was due to an inactivation and reactivation of the stretch-activated channels at the apex of the outer hair cells of the cochlea. The time constants of the multi-exponential onset and recovery do not appear to depend on the duration of the overstimulation, but the exponential coefficients do. A simple kinetic model of the onset and recovery is described (for more detail see Patuzzi (1998)). It is suggested that the rapid recovery in the first 5 min after exposure is due to a short-lived disruption of the synapses between the inner hair cells and the primary afferent neurones. Intermittent exposures were found to produce much less TTS than continuous tones, and this reduction was found to be inconsistent with the Equal Energy Hypothesis, in that the TTS produced by intermittent tones was much less than predicted using the Equal Energy model, and the recovery time course was also different from that expected from a shorter exposure to a continuous tone of equal energy.

Acoustic Stimulation↗
PubMed1998

A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels.

A model of the temporary threshold shift (TTS) following loud sound is presented based on inactivation of the mechano-electrical transduction (MET) channels at the apex of the outer hair cells (OHCs). This inactivation is assumed to reduce temporarily the OHC receptor current with a consequent drop in the mechanical sensitivity of the organ of Corti. With acoustic over-stimulation some of the hair cells' MET channels are assumed to adopt one of three closed and non-transducing conformations or 'TTS states'. The sound-induced inactivation is assumed to occur because the sound makes the TTS states more energetically favourable when compared with the transducing states, and the distribution between these states is assumed to depend on the relative energies of the states and the time allowed for migration between them. By lumping the fast transducing states (one open and two closed) into a single transducing 'pseudo-state', the kinetics of the inactivation and re-activation processes (corresponding to the onset and recovery of TTS) can be described by a four-state kinetic model. The model allows an elegant description of the onset and recovery of TTS time-course in a human subject under a variety of continuous exposure conditions, and some features of intermittent exposure as well. The model also suggests that recovery of TTS may be accelerated by an intermittent tone during the recovery period which may explain some variability TTS in the literature. Other implications of the model are also discussed.

Acoustic Stimulation↗
PubMed1993

Otoacoustic emissions and the categorization of cochlear and retro-cochlear lesions.

There are only some cochlear and retro-cochlear lesions that could be detected using a simple measurement of otoacoustic emissions. A simple description of the various lesions that lead to hearing loss and disruption of emissions is presented, a basis for categorizing cochlear and retro-cochlear lesions is discussed, and the types of clinical symptoms likely to be associated with each type of lesion are outlined.

Acoustic Stimulation↗
PubMed1992

Additivity of threshold elevations produced by disruption of outer hair cell function.

We present a simple model describing the additivity of hearing loss in the mammalian cochlea produced by disruption of the outer hair cell transduction processes. The validity of this model has been tested experimentally in the guinea-pig by inducing threshold elevations using two simultaneous cochlear manipulations, including acoustic overstimulation, two-tone suppression, low-frequency acoustic biasing of the cochlear partition and electrical stimulation of the medial olivo-cochlear system of efferent fibres. The results of these experiments suggest that the model presented is an adequate description, within the measurement error of our experiments, of the hearing losses produced.

Acoustic Stimulation↗
PubMed1990

Does electrical stimulation of the crossed olivo-cochlear bundle produce movement of the organ of Corti?

Low-frequency microphonic waveforms have been recorded in the basal turn of the guinea pig cochlea with and without electrical stimulation of the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle. Stimulation of the COCB increased the amplitude of the microphonic waveforms as described previously, but did not alter the shape of the waveforms markedly. The changes observed with COCB stimulation are consistent with a reduction in the impedance of the basolateral wall of the outer hair cells by about 50%, and possibly a 20% increase in the vibration of the organ of Corti at low frequencies, but suggest little or no change in the operating point on the transfer curve relating deflection of the hair bundles to the receptor current through the hair cells. It therefore seems that if slow contraction of the outer hair cells occurs during acute efferent stimulation in vivo, then it produces only a small deflection of the outer hair cell stereocilia, equivalent to a transverse displacement of the organ of Corti of less than 1.5 nm.

Action Potentials↗
PubMed1989

Stimulus-related potassium changes in the organ of Corti of guinea-pig.

1. Potassium concentration was measured with double-barrelled K+-selective microelectrodes within the organ of Corti in the first turn of the guinea-pig cochlea. 2. Penetration of the electrode from scala tympani through the basilar membrane was accompanied by an increase in K+ resting level from 3.0 mmol/l in perilymph to 3.4 mmol/l in cortilymph (n = 8). K+ resting level was not significantly different in various extracellular regions of the organ of Corti. On penetration of the cuticular plate, the K+ level reached 140 mmol/l simultaneously with the occurrence of a +80 mV endocochlear potential. Impalement of hair cells and supporting cells was accompanied by an increase in K+ level, but intracellular K+ level was not systematically measured. 3. Stimulation with pure tones over the frequency range 500 Hz to 25 kHz produced changes in the K+ level in the organ of Corti. The magnitude of these changes was dependent on stimulus frequency and intensity. At high sound intensities the K+ level in the tunnel of Corti could increase by typically 1 mmol/l, while a maximum increase of 3 mmol/l with respect to the resting level was observed immediately adjacent to inner hair cells. 4. During brief exposures to moderate intensity, pure tone acoustic stimulation (10 s, less than 80 dB SPL (sound pressure level] of frequency 4 kHz or greater the K+ level in the extracellular fluid of the organ of Corti rose monotonically to a steady peak level. On cessation of the stimulus the K+ level fell monotonically with a time constant of about 2 s to a level close to the pre-stimulus level. In some cases this level was slightly above the pre-stimulus level. 5. For brief exposures to moderate intensity sound (10 s, less than 80 dB SPL) the extracellular potential in the organ of Corti became more positive. The amplitude of this sound-evoked change adapted during stimulation to a level approximately one-fifth of its initial value. Upon cessation of the stimulus the potential fell transiently below its pre-stimulus level, before recovering to that level. The time constant of these changes was between 2 and 3 s. 6. Iso-response tuning curves for the sound-evoked elevation in K+ level in the organ of Corti in animals in good condition were similar to iso-rate tuning curves for primary afferent fibres reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1986

Basilar membrane measurements and the travelling wave.

From the original measurements of G. von Békésy (1942) until a few years ago, the basilar membrane was considered to undergo simple passive linear vibration. Recent measurements have completely altered this notion. It is now known that the BM is highly non linear and very sharply tuned. Indeed, BM can now account for most of the properties of the eighth nerve response to sound. The non linearity can be approximated by a hyperbolic function and appears to be part of an active process in the outer hair cell. At the characteristic frequency, CAP threshold (10 dB SPL) corresponds to 0.3 nm motion and the non linearity shows half saturation at 10 nm. The sigmoid shape of the full range BM input-output curve is due to the combination of a less sensitive linear passive component with the added sensitivity of the active non linear function. A hyperbolic input-output function is also present in the cochlear microphonics, and at low frequencies the half saturation value again corresponds to 10 nm BM displacement. With induced threshold loss (e.g. noise trauma) the nonlinearity disappears from the BM, but is still present in the CM. This suggests that the pathology is in the active mechanical feedback process, rather than in the receptor system. It appears that BM mechanics at low amplitudes near the resonant frequency is controlled by a nonlinear mechano-electrical transducer followed by a vulnerable, linear, active mechanism (electro-mechanical?) feeding back in positive phase onto BM vibration.

Animals↗
PubMed1986

Velocity and displacement coupling of mammalian inner hair cells and the mechanical resonance of the free-standing stereocilia.

Some controversy still exists as to whether the inner hair cells of the mammalian cochlea respond to the velocity or displacement of the basilar membrane or to a combination of these over their operating frequency range. A comparison between the nonlinear properties of the receptor potentials within inner hair cells of the basal turn of the guinea pig cochlea and the potentials recorded within the scala media of the same animals for stimulus frequencies between 200 and 3,200 Hz provides evidence that these inner hair cells change from velocity sensitivity to displacement sensitivity at about 1,000 Hz. We infer from this that viscosity within the subtectorial space is high enough to preclude mechanical resonance of the freestanding stereocilia of these cells as a frequency-selective mechanism within the mammalian cochlea.

Acoustic Stimulation↗
PubMed1984

The modulation of the sensitivity of the mammalian cochlea by low frequency tones. I. Primary afferent activity.

The neural activity of single cells within the spiral ganglion of the first turn of the guinea pig cochlea has been recorded. Period histograms of the spike activity have been collected. The histograms were synchronised with a loud low frequency tone (40 Hz) presented at a constant intensity below the threshold of the cells to phase locking. The activity evoked by a continuous high frequency tone within the tip of the frequency threshold curve was modulated by the presence of a subthreshold low frequency tone. Suppression of this evoked activity was observed for low frequency displacements of the cochlear partition towards scala tympani, and potentiation was observed for moderate displacements towards scala vestibuli. At higher intensities of the low frequency tone suppression is also observed for peak displacements of the partition towards scala vestibuli. The changes to these histograms with increases in the intensity of the high frequency tone are described. Hysteresis, flattening of the histograms at high intensities and nonmonotonic growth of firing rate at certain phases of the low frequency tone were observed. These changes are believed to be due to fast adaptation of the neural response rather than similar changes to the d.c. receptor potential within the inner hair cells that the neurons innervate.

Acoustic Stimulation↗
PubMed1984

The modulation of the sensitivity of the mammalian cochlea by low frequency tones. III. Basilar membrane motion.

The simultaneous presentation of an intense low frequency tone and a moderate intensity high frequency tone produced modulation of the high frequency motion of the cochlear partition in the first turn of the guinea pig cochlea. This modulation was in synchrony with the displacement caused by the low frequency tone. Maximum reduction in mechanical sensitivity was observed for peak displacements towards scala tympani, whereas a less pronounced reduction was observed for peak displacements towards scala vestibuli. Modulation was reduced or absent for high frequency tones more than an octave below the characteristic frequency of the mechanical tuning curve and was absent post mortem.

Acoustic Stimulation↗