Abstract
Intracellular calcium mobilization of isolated guinea pig cochlear outer hair cells (OHCs) was investigated using thimerosal, a -SH group oxidizing agent, and fura-2 fluorescence ratio imaging microscopy. In the presence of thimerosal, intracellular Ca 2+ concentrations ([Ca 2+ ] i ) of OHCs were elevated in a dose-dependent manner. Even in Ca 2+ -free medium, Ca 2+ response was still induced. The effects of thimerosal on [Ca 2+ ] i were completely blocked and reversed by dithiothreiotol (DTT). Neither 1-100 w M ryanodine nor 5-20 mM caffeine altered the effects of thimerosal. Pretreatment with pertussis toxin (PTX) for 30 min did not affect the thimerosal-induced increase in [Ca 2+ ] i . The increase in [Ca 2+ ] i when Ca 2+ was added during thimerosal application in Ca 2+ -free medium was almost completely blocked by 500 w M LaCl3, while nifedipine did not inhibit further increase in [Ca 2+ ] i caused by thimerosal. Thus, oxidation of the -SH group of the OHC membrane can induce a Ca 2+ release from intracellular Ca 2+ stores, which are ryanodine- and caffeine-insensitive, and Ca 2+ influx through non-specific Ca 2+ channels, but not the nifedipine-sensitive Ca 2+ channels. The possible oxidation of -SH group gated Ca 2+ channels in OHCs is worthy of further study.
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