Photoreceptor channel activation: interaction between cAMP and cGMP.

cAMP activates a current in excised patches from rod outer segments. The current at saturating concentrations of cAMP is approximately 25% of the current activated with 200 microM cGMP, the terminal cytoplasmic messenger in phototransduction. The K0.5 for cAMP is greater than 1.5 mM, and the index of cooperativity is approximately 1.4. cAMP activates the same population of channels as activated by cGMP since currents in the presence of both nucleotides are less than the sum of the individual responses. When increasing concentrations of cAMP, less than its K0.5, are added to a fixed, subsaturating concentration of cGMP, cAMP significantly enhances the total current compared with the current produced by cGMP alone. These results are predicted by a three-site, linear, sequential binding scheme where either cAMP or cGMP may bind to the same site on the channel. At approximately 5 microM cGMP, which is estimated to be the steady-state dark level in vertebrate photoreceptors, cAMP between 1 and 100 microM produces a large increase in the photoreceptor current. A possible physiological role for cAMP-cGMP interaction in phototransduction is discussed.