We report here the first evidence that ATP depolarizes the outer hair cells isolated from guinea-pig cochlea and activates a large cation channel. The outer hair cells were dissociated mechanically after enzyme treatment. Drugs were applied by a rapid concentration-jump technique. The ATP-gated channel was permeable for both mono and divalent cations. The relative permeability was in the order of Ca2+> > Li+> Na+> Cs+> > choline+. The potency of ATP agonists was ATP> > ADP> AMP-PNP> α, β-methylene ATP=β, γ-methylene ATP, indicating that the ATP-gated channel is a large cation channel and is classified as P2 subtype of the purinergic receptor.
