Comparison of the effects of trimethyltin on the intracellular calcium levels in spiral ganglion cells and outer hair cells.
Cochlear impairment by trimethyltin chloride (TMT), a potential contaminant of marine paints and polyvinyl chloride tubing, has been well demonstrated. Its toxic effect on the inner hair cells (IHC)-spiral ganglion cell (SGC) unit occurs almost immediately while disruption of outer hair cell (OHC) function does not occur until several hours after exposure. In this experiment, OHCs and SGCs from pigmented guinea pigs were tested in vitro to determine the role of enhanced intracellular calcium [Ca2+]i levels in TMT ototoxicity and to determine the sources of enhanced [Ca2+]i. The latter was determined by experiments using artificial perilymph without Ca2+ and by use of the Ca2+ channel blocker, nifedipine. The data show that TMT elevates [Ca2+]i in both OHC and SGC. The elevation of [Ca2+]i in SGC is much more rapid and larger than that in OHC. The elevation of [Ca2+]i in SGC can be attenuated by removing Ca2+ from artificial perilymph or pretreating with nifedipine, but neither of these treatments is effective in OHC. The results suggest that TMT disrupts intracellular storage of Ca2+ in OHCs and SGCs, but that is also enhancing influx of Ca2+ from extracellular sources in the SGCs.
Liu
Y
Y
College of Pharmacy, Toxicology Program, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Fechter
L D
LD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005453:Fluorescence; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D013136:Spiral Ganglion / Q000378:metabolism*; D013997:Time Factors; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D014298:Trimethyltin Compounds; C046488:trimethyltin; D009543:Nifedipine; D002118:Calcium