In order to study the interactions between cytoplasmic calcium concentration ([Ca2+]i) and light in modulating the responses of rod photoreceptors, [Ca2+]i was held at different levels by manipulating Ca2+ fluxes across the outer segment membrane. 2. If [Ca2+]i was reduced by the removal of external Ca2+ in the continued presence of Na+, and then held near this reduced level by exposure to 0 Ca(2+)-0 Na+ solution, the onset of the recovery phase of the response to a bright flash delivered just before the return to Ringer solution was accelerated, much as is the case during light adaptation, provided that precautions were taken to minimize Na+ influx. 3. If the rod was first allowed to adapt to steady light, [Ca2+]i held near the appropriate light-adapted level by superfusion with 0 Ca(2+)-0 Mg(2+)-0 Na+ solution and the light extinguished, the onset of the recovery phase of the bright flash response varied with the original background intensity in the same way as in the continued presence of steady light. These results indicate that reduction of [Ca2+]i is sufficient to induce this manifestation of light adaptation in darkness. 4. When [Ca2+]i was held at a reduced level in darkness, not only was the sensitivity to dim flashes reduced, but the response rising phase was also delayed and its amplitude increased supralinearly with flash intensity, neither of which changes is seen during light adaptation. However, similar changes in response kinetics resulted when [Ca2+]i was held near its normal dark level and the phosphodiesterase was partially inhibited by 3-isobuty-1-methylxanthine (IBMX), suggesting that they arose indirectly from an elevated cyclic GMP concentration rather than from a direct effect of Ca2+. 5. If [Ca2+]i was held near the normal dark level and bright steady light presented, the circulating current was completely suppressed. Partial inhibition of the phosphodiesterase by superfusion with 0 Ca(2+)-0 Na+ solution including IBMX resulted in restoration of the circulating current. Dim flash responses recorded under these conditions exhibited kinetics similar to those recorded in 0 Ca(2+)-0 Na+ solution in darkness, in contrast to the response acceleration seen when [Ca2+]i was held near the appropriate light-adapted level. These results indicate that the kinetics of the flash response depend on [Ca2+]i rather than on the steady light intensity.
