Nitric oxide inhibits adenosine 5′-triphosphate-induced Ca2+ response in inner hair cells of the guinea pig cochlea

To investigate the interaction between Ca 2+ and nitric oxide (NO) in inner hair cells of the guinea pig cochlea (IHCs), the extracellular adenosine 5′-triphosphate (ATP)-induced NO production and the effects of NO on ATP-induced increase of intracellular Ca 2+ concentrations ([Ca 2+ ] i ) were investigated in IHCs using the NO-sensitive dye DAF-2 and the Ca 2+ -sensitive dye Fura-2. Extracellular ATP induced an increase in DAF-2 fluorescence, which thus indicates NO production in IHCs. The ATP-induced NO production was mainly due to Ca 2+ influx through the activation of P2 receptor. l -N G -nitroarginine methyl ester, a NO synthesis inhibitor, enhanced the ATP-induced [Ca 2+ ] i increase in IHCs while S -nitroso- N -acetylpenicillamine, a NO donor, inhibited it. We conclude that NO inhibits the ATP-induced [Ca 2+ ] i increase in IHCs by a negative-feedback mechanism.