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.