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

Abstract

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.