Trimethyltin disrupts N1 sensitivity, but has limited effects on the summating potential and cochlear microphonic.
Trimethyltin (TMT), a model neurotoxicant, has previously been demonstrated to disrupt auditory thresholds in laboratory subjects. In this experiment we characterized the potency of this ototoxicant by means of a dose response study and then evaluated the functional effects of TMT administration when tone-bursts were presented at supra-threshold levels. Guinea pigs were anaesthetized and prepared for electrophysiological measurement of the compound action potential (CAP) and cochlear microphonic (CM). Subsequently averaged wave forms generated by tone-bursts of 0-80 dB SPL were evaluated in order to calculate both a N1 and a summating potential (SP) input-output function. We show that TMT at doses as low as 0.2 mg/kg produce elevations in N1, but not in the CM isopotential curve. Using exposures to 0.5 mg/kg TMT we show a profound reduction in the slope of the N1 input-output curve, but no shift in the SP. The results are consistent with the hypothesis that TMT disrupts function at the synapse between the inner hair cell and the Type 1 spiral ganglion cell.
Fechter
L D
LD
Toxicology Program, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Liu
Y
Y
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects* / Q000502:physiology; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D004594:Electrophysiology; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects; D013136:Spiral Ganglion / Q000187:drug effects; D014298:Trimethyltin Compounds / Q000633:toxicity*
D014298:Trimethyltin Compounds; C046488:trimethyltin