The actions of dopamine receptors in the guinea pig cochlea.

Dopamine, a major lateral olivocochlear efferent neurotransmitter, exerts both excitatory and inhibitory effects on the central nervous system depending on the receptor involved. We investigated the effects of different dopamine receptors on the cochlea by perilymphatic perfusion with D(1/5), D(2) and D(3) receptor agonists and antagonists and recording neural and hair cell responses (compound action potential - CAP; summating potential - SP) before, during and after perfusions. The D(1/5) agonist resulted in marked suppression of CAP amplitudes whilst leaving SP amplitudes unchanged, suggesting an inhibitory action of these receptors on afferent dendrites. The D(1/5) antagonist had little or no effect, suggesting that there is no influence of tonic dopamine release on these receptors. In contrast, perfusing a D(2) receptor antagonist resulted in marked suppression of CAP suggesting an excitatory action of the receptors and a strong influence of tonic dopamine release on the D(2) receptors. The D(2) agonist had little effect, implying that tonic dopamine release is maximally activating this class of dopamine receptors. D(2) antagonists resulted in reduction of SP, cochlear microphonic and distortion product otoacoustic emission amplitudes, suggesting that D(2) receptor action is not confined to afferent dendrites. Perfusion with D(3) agonists and antagonists had no effect.

Long term effects of BAPTA in scala media on cochlear function.

BAPTA was iontophoresed or allowed to diffuse into the scala media of the first turn of the guinea pig cochlea via pipettes inserted through the round window and basilar membrane. Cochlear action potential (CAP) thresholds for basal turn frequencies were elevated, scala media cochlear microphonic in response to a 207Hz tone were drastically reduced and the distortion products 2f1-f2 and f2-f2 in response to primaries set at 18 and 21.6kHz were eliminated or severely reduced. The animals were recovered and the above measurements repeated between 24 and 240h after the application of BAPTA. In all animals thresholds for basal turn frequencies remained elevated, and the distortion components were severely reduced. The endolymphatic potential (EP), measured through the basilar membrane on recovery, was not significantly different from the values measured before BAPTA was applied. If the effect of BAPTA, in lowering endolymphatic Ca(2+) concentration, is restricted to the destruction of tip links, as has been shown in many other preparations, then these results suggest that this effect has permanent consequences, either because the tip links failed to regenerate or because their destruction precipitated the degeneration of OHCs. These results may have a bearing on the mechanisms behind permanent threshold shift.

Primary afferent and cochlear nucleus contributions to extracellular potentials during tone-bursts.

Gross electrical responses to tone bursts were measured in the guinea pig with electrodes located in scala tympani (ST) and scala vestibuli (SV) of the cochlea, on the central portion of the VIIIth nerve fibres in the internal auditory meatus, and on the surface of the cochlear nuclear complex (CN). Intracochlear perfusion of pharmacological blockers of neural and postsynaptic activity as well as aspiration of parts or all of the CN were used to dissect the origin of the many components of the gross responses. It was shown that single-ended recordings from either ST or SV or those derived from the sum of the ST and SV responses not only contain mixed responses from the auditory nerve fibres and cochlear hair cells, but are contaminated or modified by neural activity central to the internal auditory meatus, probably in various parts of the CN. Differential recordings between ST and SV were relatively uncontaminated by such activity. Recordings from central locations were largely uncontaminated by potentials from cochlear hair cells. These results suggest that a revised and extended system of nomenclature for the different components of the gross cochlear potentials is necessary, and interpretation of such potentials needs to take into account multiple central as well as peripheral generators.