[Thiol reagent thimerosal-induced Ca2+ mobilization in isolated guinea pig cochlear outer hair cells].
OBJECTIVE
To understand mechanism of cochlear outer hair cells (OHCs) intracellular Ca2+ mobilization further.


METHODS
Intracellular calcium of isolated guinea pig was investigated using thimerosal, a--SH group oxidizing agent, and fura-2 fluorescence ratio imaging microscopy.


RESULTS
In the presence of thimerosal, intracellular Ca2+ concentrations ([Ca2+]i) of OHCs were elevated in a dose-dependent manner. Even in Ca(2+)-free medium, Ca2+ response was still induced. The effects of thimerosal on [Ca2+]i were completely blocked and reversed by (DTT). Neither 1-100 mumol/L ryanodine nor 5-20 mmol/L caffeine altered the effects of thimerosal. Pretreatment with pertussis toxin (PTX) for 30 min did not affect the thimerosal-induced increase in [Ca2+]i The increase in [Ca2+]i when Ca2+ was added during thimerosal application in Ca(2+)-free medium was almost completely blocked by 500 mol/L LaCl3, while nifedipine did not inhibit further increase in [Ca2+]i caused by thimerosal.


CONCLUSIONS
Oxidation of the -SH group of the OHC membrane can induce a Ca2+ release from intracellular Ca2+ stores, which are ryanodine- and caffeine-insensitive, and Ca2+ influx through non-specific Ca2+ channels, but not the nifedipine-sensitive Ca2+ Channels. The possible oxidation of--SH group gated Ca2+ channels in OHCs are worthy of further study.
Chen
L
L
Department of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, China. LaneChen@bigfoot.com
Jiang
S
S
Yang
W
W
Han
D
D
Yuan
T
T
Shan
X
X
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013849:Thimerosal / Q000494:pharmacology*
D013439:Sulfhydryl Reagents; D013849:Thimerosal; D002118:Calcium